Imidazole derivatives and preparation thereof

ABSTRACT

Novel imidazole of the formula: ##STR1## wherein Ring A is pyridyl group or a substituted pyridyl group; Ring B is phenyl group or a substituted phenyl group; R 1  and R 2  are hydrogen atom or are combined together to form a group of the formula: --(CH 2 ) q  --; m is 1 or 2; n is 0, 1 or 2; and q is 3 or 4, or a salt thereof are disclosed. Said derivative (I) and a salt thereof are useful as anti-ulcer agents.

The instant application is a divisional of co-pending U.S. patentapplication Ser. No. 07/372,534 filed June 28, 1989, now U.S. Pat. No.4,996,217, which in turn was a continuation-in-part of co-pending U.S.patent application Ser. No. 122,286, filed Nov. 18, 1987, now abandoned.

This invention relates to a novel imidazole derivative and processes forpreparing same. More particularly, it relates to an imidazole derivativeof the formula: ##STR2## wherein Ring A is pyridyl group or asubstituted pyridyl group, Ring B is phenyl group or a substitutedphenyl group; R¹ and R² are hydrogen atom or are combined together toform a group of the formula: -(CH₂)_(q) -; m is 1 or 2; n is 0, 1 or 2;and q is 3 or 4, or a salt thereof.

Excessive gastric acid secretion is one the of causative factors ofpeptic ulcer diseases such as gastric ulcer and duodenal ulcer. Sincethe acid secretion by gastric parietal cells is known to be induced byhistamine, acetylcholine or gastrin, cholinergic receptor blockers(e.g., atropine) and histamine H₂ -receptor blockers (e.g., cimetidine)which antagonize these stimuli in living tissues have been used fortreatment of such ulcer diseases [Medicina, 23(4) 560-565 (1986)].

Moreover, benzimidazole compounds such as omeprazole have been recentlyfound to show the antisecretory effects due to their inhibitory effecton the enzymatic activity of H⁺ /K⁺ ATPase (i.e., the enzyme which playsan important role in concentration and/or secretion of gastric acid)(Japanese Patent Publication (unexamined) No. 141783/1979).

However, among these known drugs, cholinergic receptor blockers arestill unsatisfactory for clinical use because of strong toxicity (e.g.,atropine toxicosis). Cimetidine, one of the histamine H₂ receptorblockers, is also known to have unfavorable side effects such asanti-androgen effect and prolactin release-stimulating effect.

As a result of various investigations, we have now found that thecompound (I) of the present invention and a salt thereof show potentinhibitory effect against gastric acid secretion and is useful fortherapeutic treatment or prophylaxis of peptic ulcer diseases. Forexample, when the effect of a test compound on gastrin-induced gastricacid secretion was examined by oral administration to rats, each one of1-(2-pyridyl)-2-[2-(1-pyrrolyl)benzylsulfinyl]imidazole,1-(3-methyl-2-pyridyl)-2-[2-(dimethylamino)benzylsulfinyl]imidazole and1,4,5,6-tetrahydro-1-(2-pyridyl)-2-[2-(diethylamino)benzylsulfinyl]cyclopenta[d]imidazoleat the dose of 30 mg/kg showed more than 70% decrease in gastric acidsecretion as compared with non-administered group of rats. On the otherhand, when the effect of a test compound on the enzyme activity of H⁺/K⁺ ATPase prepared from the porcine gastric mucosa was examined, IC₅₀(i.e., the concentration required to induce 50% inhibition of saidenzymatic activity) of1,4,5,6-tetrahydro-1-(2-pyridyl)-2-[2-(diethylamino)benzylsulfinyl]cyclopenta[d]imidazolewas about 10 μM and IC₅₀ of1-(2-pyridyl)-2-[2-(cyclohexylamino)benzylsulfinyl]imidazole and1-(4-methoxy-6-methyl-2-pyridyl)-2-[2-(diethylamino)benzylsulfinyl]imidazolewere less than 10 μM.

Examples of the compounds of the present invention are those of theformula (I) in which Ring A is a 2-, 3- or 4-pyridyl group which mayoptionally have one or two substituent(s) selected from a halogen atomsuch as chlorine atom or bromine atom, a lower alkyl group such asmethyl group or ethyl group, a lower alkoxy group such as methoxy group,ethoxy group or isopropoxy group, a phenyl-lower alkoxy group such asbenzyloxy group, nitro group, amino group, a lower alkanoylamino groupsuch as acetylamino group or propionylamino group, a N-loweralkyl-N-lower alkanoylamino group such as N-methyl-N-acetylamino group,a mono- or di(lower alkyl)amino group such as methylamino group,ethylamino group, dimethylamino group or diethylamino group, a loweralkanoyloxy group such as acetoxy group, cyanide group, atrihalogeno-lower alkyl group such as trifluoromethyl group, atrihalogeno-lower alkoxy group such as 2,2,2-trifluoroethoxy group, alower alkenyloxy group such as allyloxy group, and hydroxy group; Ring Bis a phenyl group which may optionally have one substituent selectedfrom nitro group, amino group, a mono- or di(lower alkyl)amino groupsuch as methylamino group, ethylamino group, dimethylamino group,diethylamino group or dipropylamino group, a lower alkanoylamino groupsuch as acetylamino group or propionylamino group, phenylamino group, acycloalkylamino group such as cyclohexylamino group, a N-(tri-loweralkylphenyl)sulfonylamino group such as(2,4,6-trimethylphenyl)sulfonylamino group, a N-lower alkyl-N-(tri-loweralkylphenyl)sulfonylamino group such asN-methyl-N-(2,4,6-trimethylpheny)sulfonylamino group, a N-loweralkyl-N-phenylamino group such as N-methyl-N-phenylamino group orN-ethyl-N-phenylamino group, a di(lower alkyl)amino-loweralkylideneamino group such as dimethylamino-methylideneamino group, adi(lower alkyl)amino-lower alkyl group such as dimethylaminomethyl groupor diethylaminomethyl group, a N-lower alkyl-N-lower alkanoylamino groupsuch as N-methyl-N-acetylamino group, a lower alkoxy group such asmethoxy group or ethoxy group, an arylcarbonylamino group such asbenzoylamino group, a lower alkylsulfonylamino group such asmethanesulfonylamino group, formylamino group, a loweralkoxycarbonylamino group such as methoxycarbonylamino group orethoxycarbonylamino group, phthalimido group and a nitrogen-containing5- or 6-membered hetero monocyclic group such as morpholino group,imidazolyl group, pyrrolyl group, pyrrolidinyl group or piperidinogroup; R¹ and R² are hydrogen atom or are combined together to formtrimethylene group or tetramethylene group; m is 1 or 2; and n is 0, 1or 2.

Among them, preferred examples of the compound of the invention arethose of the formula (I) in which Ring A is 2-or 4- pyridyl group whichmay optionally have one or two substituent(s) selected from a C₁₋₄ alkylgroup, a C₁₋₄ alkoxy group and a C₇₋₈ phenylalkoxy group; Ring B isphenyl group which may optionally have one substituent selected fromamino group, a mono(C₁₋₄ alkyl)amino group, a di(C₁₋₄ alkyl)amino group,a C₁₋₄ alkanoylamino group, morpholino group, pyrrolyl group andpiperidino group; R¹ and R² are hydrogen atom or are combined togetherto form trimethylene group; m is 1; and n is 0, 1 or 2.

More preferred examples of the compound of the invention are those ofthe formula (I) in which Ring A is 2- or 4-pyridyl group, a 3-, 4- or5-(C₁₋₄ alkoxy)-2-pyridyl group, a 3-, 4-, 5- or 6-(C₁₋₄alkyl)-2-pyridyl group, a 3-(C₇₋₈ phenylalkoxy)-2-pyridyl group, a2-(C₁₋₄ alkyl)-4-pyridyl group or a 4-(C₁₋₄ alkoxy)-6-(C₁₋₄alkyl)-2-pyridyl group; Ring B is phenyl group, 2-morpholinophenylgroup, 2-aminophenyl group, a 2-mono(C₁₋₄ alkyl)aminophenyl group, a2-di(C₁₋₄ alkyl)aminophenyl group, 2-(pyrrolyl)phenyl group,2-piperidino group or a 2-(C₁₋₄ alkanoyl)aminophenyl group; R¹ and R²are hydrogen atom or are combined together to form trimethylene group; mis 1; and n is 0, 1 or 2.

Most preferred examples of the compound of the invention are those ofthe formula (I) in which Ring A is 2-pyridyl group, a 3- or 4-(C₁₋₄alkyl)-2-pyridyl group or 3-(C₁₋₄ alkoxy)-2-pyridyl group; Ring B isphenyl group, 2-aminophenyl group, 2-mono(C₁₋₄ alkyl)aminophenyl group,a 2-di(C₁₋₄ alkyl)aminophenyl group or 2-(1-pyrrolyl)phenyl group, R¹and R² are hydrogen atom or are combined together to form trimethylenegroup; m is 1; and n is 0.

Other most preferred examples of the compound of the invention are thoseof the formula (I) in which Ring A is 2-pyridyl group, 3- or 4-(C₁₋₄alkyl)-2-pyridyl group or 3-(C₁₋₄ alkoxy)-2-pyridyl group; and Ring B isphenyl group, 2-aminophenyl group, 2-mono(C₁₋₄ alkyl)aminophenyl groupor 2-di(C₁₋₄ alkyl)aminophenyl group; R¹ and R² are hydrogen atom; m is1 and n is 0.

Other most preferred examples of the compound of the invention are thoseof the formula (I) in which Ring A is 3-or 4-methyl-2-pyridyl group or3-methoxy-2-pyridyl group; Ring B is 2-aminophenyl group,2-dimethylaminophenyl group or 2-diethylaminophenyl group; R¹ and R² arehydrogen atom; m is 1 and n is 0.

While the compound (I) of the present invention in which m is 1 mayexist in the form of two optically active isomers due to an asymmetricsulfoxide group, the present invention includes within its scope eitherone of these isomers and a mixture thereof.

According to the present invention, the compound (I) or a salt thereofcan be prepared by the steps of:

i) condensing a mercaptoimidazole compound of the formula: ##STR3##wherein Ring A, R¹, R² and n are the same as defined above, or a saltthereof with a toluene compound of the formula: ##STR4## wherein X is areactive residue and Ring B is the same as defined above, or a saltthereof,

ii) oxidizing the resultant product of the formula: ##STR5## whereinRing A, Ring B, R¹, R² and n are the same as defined above, and

iii) if required, further converting the product into a salt thereof.

Alternatively, the compound (I) in which R¹ and R² are combined togetherto form a group of the formula: -(CH₂)_(q) - (wherein q is the same asdefined above) or a salt thereof can be prepared by the steps of:

iv) dehydrating a compound of the formula: ##STR6## wherein R¹¹ and R²¹are combined together to form a group of the formula: -(CH₂)_(q) - andRing A, Ring B, q and n are the same as defined above,

v) oxidizing the resultant product, and

vi) if required, further converting the product into a salt thereof.

The condensation of the mercaptoimidazole compound (III) and the toluenecompound (IV) can be conducted in the presence or absence of an acidacceptor in an inert solvent. Any groups which can form a C--S bondthrough reaction with a mercapto group can be used as the reactiveresidue "X" of the toluene compound (IV). Such reactive residue Xincludes, for example, a halogen atom, an alkylsulfonyloxy group (e.g.,methylsulfonyloxy group), an arylsulfonyloxy group (e.g.,toluenesulfonyloxy group, benzenesulfonyloxy group) and the like. Thecompound (IV) which has amino group, a N-substituted amino group and thelike on the benzene ring may, if required, be used for the reaction inthe form of an organic or inorganic acid addition salt such ashydrochloride, hydrobromide, sulfate, nitrate, formate, oxalate ormethanesulfonate. On the other hand, the compound (III) may, ifrequired, be used for the reaction in the form of an organic orinorganic acid addition salt (e.g., hydrochloride, hydrobromide,sulfate, nitrate, formate, oxalate or methanesulfonate), an alkali metalsalt (e.g., sodium salt or potassium salt), an alkaline earth metal salt(e.g., calcium salt or magnesium salt), and a quaternary ammonium salt(e.g., tetramethylammonium salt). A lower alkanol, dimethylformamide,dimethylsulfoxide, water and the mixture thereof are suitable as thesolvent. Suitable examples of the acid acceptor include inorganic basessuch as an alkali metal hydroxide, an alkali earth metal hydroxide, analkali metal carbonate, an alkali metal bicarbonate, an alkali metalalkoxide, an alkali metal amide, an alkali metal fluoride, an alkalimetal hydride, or organic bases such as pyridine, a tri-loweralkylamine, a lower alkyl lithium, a quaternary ammonium hydroxide(e.g., tetra n-butyl ammonium hydroxide), and the like. It is preferredto carry out the reaction at -20° C. to 170° C., especially -10° to 100°C.

On the other hand, the dehydration of the imidazole derivative (V) canbe conducted in the presence of a dehydrating agent in an inert solvent.Suitable examples of the dehydrating agent include organic acids such asformic acid, trifluoroacetic acid, p-toluenesulfonic acid,benzenesulfonic acid or camphorsulfonic acid, mineral acids such ashydrochloric acid or sulfonic acid or a mixture of a halogenating agent(e.g., phosphrus tribromide, phosphorus trichloride or phosphorusoxychloride) and a base (e.g., pyridine or triethylamine) and the like.The compound (V) may, if required, be used for the reaction in the formof an organic or inorganic acid addition salt such as hydrochloride,hydrobromide, sulfate, nitrate, formate, oxalate or methanesulfonate. Itis preferred to carry out the reaction at -20° C. to 150° C., especially-10° C. to 100° C.

The oxidation of the above-obtained compound (II) [including thedehydration product of the imidazole derivative (V)] is conducted bytreating it with an oxidative agent.

Conventional oxidative agents such as peroxy acids (e.g.,m-chloroperbenzoic acid, perbenzoic acid or peracetic acid), an alkalimetal hypochlorite, an alkali metal chlorite, an alkali metal periodate,tetra n-butyl ammonium periodate, tert.-butyl hydroperoxide,iodoxybenzene, and the like can be used for the reaction. A loweralkanol, methylene chloride, chloroform, tetrahydrofuran, dioxane, waterand the mixture thereof are suitable as the solvent. It is preferred tocarry out the reaction at -70° C. to 100° C., especially -50° C. to 20°C. In this reaction, a sulfinyl-imidazole compound (I) (m=1) is obtainedby using an equimolar amount or a little excess amount of the oxidativeagent, and a sulfonyl-imidazole compound (I) (m=2) is obtained by usingnot less than two equimolar amount of the oxidative agent.

The intermediate (II) obtained by the above-mentioned reaction is anovel compound, and the substituent(s) on the Ring A and/or B thereofmay be, if required, modified or converted to other substituent(s)before the oxidation step. For example, the compound (II) having aminogroup on the Ring A and/or B may be obtained by conventional reductionof the compound (II) having nitro group thereon, or by hydrolysis of thecorresponding N-phthalimido or N-tri lower alkylphenylsulfonylamidocompound (II). Alternatively, the compound (II) having one or twosubstituent(s) selected from a lower alkanoylamino group, a loweralkylsulfonylamino group, formylamino group, a lower alkylamino group,an arylcarbonylamino group, a lower alkoxycarbonylamino group and asubstituted phenylsulfonylamino group on the Ring A and/or B thereof maybe obtained by conventional acylation or alkylation of the compound (II)having amino group, an N-alkylamino group or an N-acylamino group onsaid Ring A and/or B.

Because of the potent inhibitory effect against gastric acid secretionand/or potent inhibitory effect on the enzymatic activity of H⁺ /K⁺ATPase, the imidazole compound (I) of the present invention and a saltthereof are useful for therapeutic treatment and/or prophylaxis ofpeptic ulcer diseases such as gastric ulcer and duodenal ulcer. Theimidazole compound (I) and a salt thereof can be used withoutunfavorable side effects such as anti-androgen or prolactinrelease-stimulating effects as observed in histamine H₂ -receptorblockers. Moreover, since the imidazole compound (I) and a salt thereofmay include a group of compounds which inhibit effectively the gastricacid secretion without affecting the enzyme activity of H⁺ /K⁺ ATPase,such compounds may be used as anti-ulcer agents which are different inmechanism of action from the known H⁺ /K⁺ ATPase inhibitors such asomeprazole.

The compound (I) can be used for pharmaceutical use either in the freeform or in the form of a salt thereof. Suitable salts of the compound(I) for pharmaceutical use include, for example, pharmaceuticallyacceptable salts such as inorganic acid addition salts (e.g.,hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate), organicacid addition salts (e.g., formate, oxalate, methanesulfonate,glucuronate), and the like. Such salts may be obtained by treating thefree base of the compound (I) with a stoichiometrically equimolar amountof the acid.

The dose of the compound (I) or a salt thereof may vary depending on theage, condition and body weight of patients, the kind and severity ofdiseases to be treated and administration route, etc, but may usually beabout 0.05 to about 50 mg/kg, preferably about 0.1 to about 20 mg/kg,per day.

The compound (I) and a salt thereof may be administered either orally orparenterally. When administrated orally, the pharmaceutical preparationmay be in the solid form such as tablets, powders, capsules orsuppositories. These preparations may contain pharmaceutical excipient,binder, diluent, disintegrator or lubricant. The pharmaceuticalpreparation for oral administration may also be in liquid form such asaqueous or oily suspension, solution, sirup or elixir. Moreover, whenadministered parenterally, the pharmaceutical preparation may be used inthe form of injections.

Concomitantly, the starting compound (III) in which R¹ and R² arehydrogen atom may be prepared by the steps of reacting a pyridinecompound of the formula: ##STR7## wherein Ring A and n are the same asdefined above, with an iso (thio) cyanate compound of the formula:

    Z═C═NCH.sub.2 CH(OR.sup.3).sub.2                   (VII)

wherein R³ is an alkyl group and Z is oxygen atom or sulfur atom, in aninert solvent, treating the thus-obtained (thio) urea compound with anorganic or inorganic acid to give the corresponding cyclic compound, andwhen Z is oxgen atom, further treating the cyclic compound with a sulfuragent such as Lawesson's Reagent(2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide),2,4-diethoxy-1,3-dithia-2,4-diphosphetane-2,4-disulfide or phosphoruspentasulfide. Alternatively, the starting compound (III) in which R¹ andR² are combined together to form a group of the formula: -(CH₂)_(q) -,(wherein q is the same as defined above) may be prepared by condensing2-aminocyclohexanone or 2-aminocyclopentanone with a compound of theformula: ##STR8## wherein Ring A and n are the same as defined above, inthe presence of triethylamine, and dehydrating the product in the samemanner as described in the dehydration reaction of the imidazolederivative (V). The starting compound (V) may be prepared by condensing2-aminocyclohexanone or 2-aminocyclopentanone with the compound (VIII)in the presence of triethylamine, and then condensing the product withthe toluene compound (IV).

Practical and presently preferred embodiments of the present inventionare illustratively shown in the following examples.

EXAMPLE 1

(1) 3.0 g of 1-(2-pyridyl)-2-mercaptoimidazole are dissolved in 50 ml ofethanol, and 16.9 ml of a 2N-aqueous sodium hydroxide solution are addedthereto under ice-cooling. 3.84 g of m-dimethylaminobenzyl chloridehydrochloride are added to the mixture and stirred at room temperaturefor 2 hours. After the solvent is distilled off, water is added to theresidue, and the mixture is extracted with ethyl acetate. The extract iswashed with water, dried and evaporated to remove the solvent. Theresidue is recrystallized from a mixture of ethyl acetate and n-hexane,whereby 3.95 g of 1-(2-pyridyl)-2-(3-dimethylaminobenzylthio)imidazoleare obtained.

Yield 75%

M.p. 79°-80° C.

(2) A solution of 3.73 g of the product obtained above in 100 ml ofmethylene chloride is cooled to -40° C. under argon gas atmosphere. 5.32g of 80% m-chloroperbenzoic acid are added thereto gradually. Themixture is stirred at the same temperature for 1 hour. The reactionmixture is washed with a saturated aqueous sodium bicarbonate solution,dried and evaporated to remove the solvent. The residue isrecrystallized from methanol, whereby 1.48 g of1-(2-pyridyl)-2-(3-dimethylaminobenzylsulfinyl)imidazole are obtained.

Yield 55%

M.p. 177°-179° C.

EXAMPLES 2 to 25

(1) The corresponding starting compounds are treated in the same manneras described in Example 1-(1) to give the compounds shown in Table 1.

                                      TABLE 1                                     __________________________________________________________________________     ##STR9##                                                                     (wherein n = 2 in Example 9, n = 1 in Example 14, and n = 0 in                Example 1 to 8, 10 to 13, and 15 to 25)                                       Ex.   Compound (II-a)                                                         Nos.  Ring A        Properties*                                               __________________________________________________________________________     2-(1)                                                                               ##STR10##    M.p. 62 to 64° C.(recrystallized from                                  n-hexane)                                                  3-(1)                                                                               ##STR11##    oil                                                        4-(1)                                                                               ##STR12##    oil; NMR, δ: 2.48(s, 3H, CCH.sub.2), 2.69(s,                            6H, N(CH.sub.3).sub.2), 3.81(s, 3H, OCH.sub.3), 4.58                          (s, 2H, SCH.sub.2) Mass(m/e): 353(M.sup.+), 134            5-(1)                                                                               ##STR13##    oil; NMR δ: 2.68(s, 6H, N(CH.sub.3).sub.2),                             4.36 (q, 2H, OCH.sub.2 CF.sub.3), 4.57(s, 2H,                                 SCH.sub.2) Mass(m/e): 408(M.sup.+), 134                    6-(1)                                                                               ##STR14##    M.p. 158 to 160° C.(recrystallized from                                methanol, chloroform and isopropyl ether)                  7-(1)                                                                               ##STR15##    oil                                                        8-(1)                                                                               ##STR16##    M.p. 51 to 53.5° C.(recrystallized from ethyl                          acetate and n-hexane)                                      9-(1)                                                                               ##STR17##                                                                                   ##STR18##                                                10-(1)                                                                               ##STR19##    oil; NMR δ: 2.67(s, 6H, N(CH.sub.3).sub.2),                             4.56(s, 2H, SCH.sub.2) Mass(m/e): 390, 388(M.sup.+),                          134                                                       11-(1)                                                                               ##STR20##    M.p. 130 to 132° C. (recrystallized from                               ethanol)                                                  12-(1)                                                                               ##STR21##    oil; NMR δ: 2.96(s, 6H, N(CH.sub.3).sub.2),                             3.96 (s, 3H, OCH.sub.3), 4.61(s, 2H, SCH.sub.2)                               Mass(m/e): 340(M.sup.+), 134                              13-(1)                                                                               ##STR22##    M.p. 70 to 72° C.(recrystallized from ethyl                            acetate and isopropyl ether)                              14-(1)                                                                               ##STR23##    oil; NMR, δ: 2.66(s, 6H, N(CH.sub.3).sub.2),                            4.38(s, 2H, SCH.sub.2), 5.08(s, 2H, NCH.sub.2)                                Mass(m/e): 324(M.sup.+)                                   15-(1)                                                                               ##STR24##    oil; NMR, δ: 2.68(s, 6H, N(CH.sub.3).sub.2),                            4.58(s, 2H, SCH.sub.2) Mass(m/e): 310(M.sup.+)            16-(1)                                                                               ##STR25##    oil; NMR, δ: 2.67(s, 6H, N(CH.sub.3).sub.2),                            4.56(s, 2H, SCH.sub.2) Mass(m/e): 344, 346(M.sup.+)       17-(1)                                                                               ##STR26##                                                                                   ##STR27##                                                18-(1)                                                                               ##STR28##    oil; NMR, δ: 2.60(s, 6H, N(CH.sub.3).sub. 2),                           4.45(s, 2H, SCH.sub.2) Mass(m/e): 310(M.sup.+)            19-(1)                                                                               ##STR29##    oil; NMR, δ: 2.57(s, 6H, N(CH.sub.3).sub.2),                            4.38(s, 2H, SCH.sub.2) Mass(m/e): 310(M.sup.+)            20-(1)                                                                               ##STR30##    M.p. 140 to 142° C.(recrystallized from                                chloroform and ethanol)                                   21-(1)                                                                               ##STR31##                                                                                   ##STR32##                                                22-(1)                                                                               ##STR33##    oil; NMR, δ: 2.68(s, 6H, N(CH.sub.3).sub.2),                            3.85(s, 3H, OCH.sub.3), 4.58(s, 2H, SCH.sub.2)                                Mass(m/e): 340(M.sup.+)                                   23-(1)                                                                               ##STR34##                                                                                   ##STR35##                                                24-(1)                                                                               ##STR36##    oil; NMR,: δ 2.63(s, 6H, N(CH.sub.3).sub.2),                            3.81(s, 3H, OCH.sub.3), 4.48(s, 2H, SCH.sub.2)                                Mass(m/e): 340(M.sup.+)                                   25-(1)                                                                               ##STR37##                                                                                   ##STR38##                                                __________________________________________________________________________      *note: NMR is measured in CDCl.sub.3                                    

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 2.

                                      TABLE 2                                     __________________________________________________________________________     ##STR39##                                                                    (wherein n = 2 in Example 9, n = 1 in Example 14, and n = 0 in                Examples 1 to 8, 10 to 13, and 15 to 25)                                      Ex. Compound(I-a)                                                             Nos.                                                                              Ring A       Properties*                                                  __________________________________________________________________________     2-(2)                                                                             ##STR40##   M.p. 122 to 124.5° C.(recrystallized from ethyl                        acetate and n-hexane)                                         3-(2)                                                                             ##STR41##   M.p. 107 to 111° C.(recrystallized from                                chloroform, isopropyl ether and n-hexane)                     4-(2)                                                                             ##STR42##   M.p. 124 to 128° C.(recrystallized from ethyl                          acetate)                                                      5-(2)                                                                             ##STR43##   M.p. 106 to 110° C.(recrystallized from ethyl                          acetate)                                                      6-(2)                                                                             ##STR44##   powder; M.p. about 60° C. NMR, δ: 2.53(s,                        6H, N(CH.sub.3).sub.2), 4.76(ABq, 2H, SCH.sub.2),                             9.30(br, 1H, OH) Mass(m/e): 342(M.sup.+)                      7-(2)                                                                             ##STR45##   M.p. 117 to 119° C.(recrystallized from                                chloroform and isopropyl ether)                               8-(2)                                                                             ##STR46##   M.p. 81.5 to 83.5° C.(recrystallized from ethyl                        acetate and n-hexane)                                         9-(2)                                                                             ##STR47##   oil; NMR, δ: 2.68(s, 6H, N(CH.sub.3).sub.2),                            4.82(ABq, 2H, SCH.sub.2)  IRν .sub.max.sup.liquid(cm.s                     up.-1): 1040(SO) Mass(m/e): 339(M.sup.+ +1)                  10-(2)                                                                             ##STR48##   M.p. 73 to 75° C.(recrystallized from chloroform                       and n-hexane)                                                11-(2)                                                                             ##STR49##   M.p. 137 to 139° C.(recrystallized from                                chloroform and n-hexane)                                     12-(2)                                                                             ##STR50##   M.p. 102 to 104° C.(recrystallized from ethyl                          acetate and n-hexane)                                        13-(2)                                                                             ##STR51##   M.p. 95.5 to 97° C.(recrystallized from ethyl                          acetate and n-hexane)                                        14-(2)                                                                             ##STR52##   M.p. 93 to 94° C.(recrystallized from ethyl                            acetate and ether)                                           15-(2)                                                                             ##STR53##   M.p. 104 to 105° C.(recrystallized from ethyl                          acetate and n-hexane)                                        16-(2)                                                                             ##STR54##   oil; NMR, δ: 2.62(s, 6H, N(CH.sub.3).sub.2),                            4.80(ABq, 2H, J=12.5Hz, SCH.sub.2)                           17-(2)                                                                             ##STR55##   oil; NMR, δ: 2.38(s, 3H, CH.sub.3), 2.63(s, 6H,                         N(CH.sub.3).sub.2), 4.85(ABq, 2H, J=12.5Hz, SCH.sub.2)       18-(2)                                                                             ##STR56##   M.p. 102 to 104° C.(recrystallized from                                chloroform and isopropyl ether)                              19-(2)                                                                             ##STR57##   oil; NMR, δ: 2.55(s, 6H, N(CH.sub.3).sub.2),                            4.83(q, 2H, J=11.5Hz, SCH.sub.2) Mass(m/e):                                   326(M.sup.+)                                                 20-(2)                                                                             ##STR58##   M.p. 133 to 135° C.(recrystallized from                                chloroform and isopropyl ether)                              21-(2)                                                                             ##STR59##   Oxalate** M.p. 96 to 100° C.(decomp.)                 22-(2)                                                                             ##STR60##   M.p. 117 to 120° C.(recrystallized from isopropyl                      alcohol and isopropyl ether)                                 23-(2)                                                                             ##STR61##   Oxalate** M.p. 82 to 84° C.(decomp.)                  24-(2)                                                                             ##STR62##   oil; NMR, δ: 2.61(s, 6H, N(CH.sub.3).sub.2), 3.83                       (s, 3H, OCH.sub.3), 4.80(ABq, 2H, J=12.5Hz, SCH.sub.2)                        Mass(m/e): 356(M.sup.+), 134                                 25-(2)                                                                             ##STR63##                                                                                  ##STR64##                                                   __________________________________________________________________________      *note: NMR is measured in CDCl.sub.3                                    

EXAMPLES 26 TO 31

(1) The corresponding starting compounds are treated in the same manneras described in Example 1-(1) to give the compounds shown in Table 3.

                                      TABLE 3                                     __________________________________________________________________________     ##STR65##                                                                    (wherein n = 0)                                                                      Compound(II-b)                                                         Ex. Nos.                                                                             Ring A      Properties*                                                __________________________________________________________________________    26-(1)                                                                                ##STR66##                                                                                 ##STR67##                                                 27-(1)                                                                                ##STR68##                                                                                 ##STR69##                                                 28-(1)                                                                                ##STR70##                                                                                 ##STR71##                                                 29-(1)                                                                                ##STR72##                                                                                 ##STR73##                                                 30-(1)                                                                                ##STR74##  oil                                                        31-(1)                                                                                ##STR75##                                                                                 ##STR76##                                                 __________________________________________________________________________      *note: NMR is measured in CDCl.sub.3                                    

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 4.

                  TABLE 4                                                         ______________________________________                                         ##STR77##                                                                    (wherein n = 0)                                                               Ex.   Compound(I-b)                                                           Nos.  Ring A        Properties*                                               ______________________________________                                        26-(2)                                                                               ##STR78##    M.p. 110 to 112° C.(recrystallized from                                ether)                                                    27-(2)                                                                               ##STR79##    M.p. 81 to 83° C.(recrystallized from ether                            and n-hexane)                                             28-(2)                                                                               ##STR80##    M.p. 99 to 100° C.(recrystallized from ethyl                           acetate and n-hexane)                                     29-(2)                                                                               ##STR81##                                                                                   ##STR82##                                                30-(2)                                                                               ##STR83##    M.p. 121 to 123° C.(recrystallized from                                isopropyl ether)                                          31-(2)                                                                               ##STR84##    M.p. 115 to 116° C.(recrystallized from                                methylene chloride and n-hexane)                          ______________________________________                                          *note: NMR is measured in CDCl.sub.3                                    

EXAMPLES 32 TO 50

(1) The corresponding starting compounds are treated in the same manneras described in Example 1-(1) to give the compounds shown in Table 5.

                  TABLE 5                                                         ______________________________________                                         ##STR85##                                                                     ##STR86##                                                                    (wherein n = 1 in Example 41, and n = 0 in Examples 32                        to 40 and 42 to 50)                                                           Ex.   Compound (II-c)                                                         Nos.  Ring A         Properties*                                              ______________________________________                                        32-(1)                                                                               ##STR87##     M.p. 138.5 to 140° C. (recrystallized from                             chloroform and n-hexane)                                 33-(1)                                                                               ##STR88##     M.p. 148 to 150° C. (recrystallized from                               chloroform and n-hexane)                                 34-(1)                                                                               ##STR89##     M.p. 148 to 151° C. (recrystallized from                               ethyl acetate and n-hexane)                              35-(1)                                                                               ##STR90##     M.p. 119 to 121.5° C. (recrystallized from                             ethyl acetate and n-hexane)                              36-(1)                                                                               ##STR91##     oil                                                      37-(1)                                                                               ##STR92##     M.p. 191 to 193° C. (recrystallized from                               chloroform and n-hexane)                                 38-(1)                                                                               ##STR93##     oil; NMR, δ: 2.91(m, 4H, NCH.sub.2), 3.80(m,                            4H, OCH.sub.2), 4.38(q, 2H, OCH.sub.2 CF.sub.3),                              4.57(s, 2H, SCH.sub.2) Mass(m/e): 450(M.sup.+), 175      39-(1)                                                                               ##STR94##     M.p. 103 to 105° C. (recrystallized from                               ethyl acetate and n-hexane)                              40-(1)                                                                               ##STR95##     oil                                                      41-(1)                                                                               ##STR96##     oil; NMR, δ: 4.39(s, 2H, SCH.sub.2), 5.04(s,                            2H, NCH.sub.2 N) Mass(m/e): 367(M.sup.+ + 1), 175        42-(1)                                                                               ##STR97##     M.p. 137 to 138° C. (recrystallized from                               ethyl acetate and n-hexane)                              43-(1)                                                                               ##STR98##     oil; NMR, δ: 2.06(s, 3H, CH.sub.3), 4.44(s,                             2H, SCH.sub.2) Mass(m/e): 366(M.sup.+), 175              44-(1)                                                                               ##STR99##     M.p. 109 to 111° C. (recrystallized from                               ethyl acetate and n-hexane)                              45-(1)                                                                               ##STR100##    M.p. 98 to 100° C. (recrystallized from ethyl                          acetate and isopropyl ether)                             46-(1)                                                                               ##STR101##    M.p. 114 to 116° C. (recrystallized from                               ethyl acetate and n-hexane)                              47-(1)                                                                               ##STR102##    M.p. 126 to 128° C. (recrystallized from                               ethyl acetate and n-hexane)                              48-(1)                                                                               ##STR103##    M.p. 124 to 126° C. (recrystallized from                               ethyl acetate and n-hexane)                              49-(1)                                                                               ##STR104##    M.p. 199 to 202° C. (recrystallized from                               chloroform and n-hexane)                                 50-(1)                                                                               ##STR105##    M.p. 112 to 113° C. (recrystallized from                               ethyl acetate, ether and n-hexane)                       ______________________________________                                         *note: NMR is measured in CDCl.sub.3                                     

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 6.

                  TABLE 6                                                         ______________________________________                                         ##STR106##                                                                   (wherein n = 1 in Example 41, and n = 0 in Examples 32                        to 40 and 42 to 50)                                                           Ex.   Compound (I-c)                                                          Nos.  Ring A         Properties*                                              ______________________________________                                        32-(2)                                                                                ##STR107##   M.p. 143 to 144.5° C. (recrystallized from                             chloroform and n-hexane)                                 33-(2)                                                                                ##STR108##   M.p. 143 to 145° C. (recrystallized from                               chloroform and n-hexane)                                 34-(2)                                                                                ##STR109##   M.p. 143.5 to 144.5° C. (recrystallized from                           chloroform and n-hexane)                                 35-(2)                                                                                ##STR110##   M.p. 139 to 141° C. (recrystallized from                               ethyl acetate and n-hexane)                              36-(2)                                                                                ##STR111##   M.p. 178 to 183° C. (recrystallized from                               chloroform, isopropyl ether and n-hexane)                37-(2)                                                                                ##STR112##   M.p. 161 to 164° C. (decomp. recrystallized                            from methanol, chloroform and n-hexane)                  38-(2)                                                                                ##STR113##   M.p. 140 to 144° C. (recrystallized from                               ethyl acetate and n-hexane)                              39-(2)                                                                                ##STR114##   M.p. 151 to 152° C. (recrystallized from                               ethyl acetate)                                           40-(2)                                                                                ##STR115##   M.p. 91 to 96° C. (recrystallized from                                 isopropyl ether)                                         41-(2)                                                                                ##STR116##   oil; NMR, δ: 4.81(ABq, 2H, SCH.sub.2),                                  5.35(ABq, 2H, NCH.sub.2 N) Mass(m/e): 383(M.sup.+ +                           1), 176                                                  42-(2)                                                                                ##STR117##   M.p. 150 to 152° C. (recrystallized from                               ethyl acetate)                                           43-(2)                                                                                ##STR118##   M.p. 129 to 130° C. (recrystallized from                               ethyl acetate and n-hexane)                              44-(2)                                                                                ##STR119##   M.p. 155.5 to 157.5° C. (recrystallized from                           chloroform and n-hexane)                                 45-(2)                                                                                ##STR120##   M.p. 135 to 137° C. (recrystallized from                               ethyl acetate)                                           46-(2)                                                                                ##STR121##   M.p. 124 to 126° C. (recrystallized from                               ethyl acetate and n-hexane)                              47-(2)                                                                                ##STR122##    M.p. 133 to 135° C. (recrystallized from                              ethyl acetate and n-hexane)                              48-(2)                                                                                ##STR123##   M.p. 130 to 132° C. (recrystallized from                               ethyl acetate and n-hexane)                              49-(2)                                                                                ##STR124##   M.p. 179.5 to 181.5° C. (recrystallized from                           chloroform and ethanol)                                  50-(2)                                                                                ##STR125##   M.p. 112 to 115° C. (recrystallized from                               ethyl acetate)                                           ______________________________________                                         *note: NMR is measured in CDCl.sub.3                                     

EXAMPLES 51 TO 58

(1) The corresponding starting compounds are treated in the same manneras described in Example 1-(1) to give the compounds shown in Table 7.

                  TABLE 7                                                         ______________________________________                                         ##STR126##                                                                    ##STR127##                                                                   (wherein n = 0)                                                               Ex.   Compound (II-d)                                                         Nos.  Ring A         Properties*                                              ______________________________________                                        51-(1)                                                                               ##STR128##    oil; NMR, δ: 1.30-1.90(m, 6H, CH.sub.2),                                2.36(s, 3H, CCH.sub.3), 2.60-3.00(m, 4H, NCH.sub.2),                          4.54(s, 2H, SCH.sub.2) Mass(m/e): 364(M.sup.+), 173      52-(1)                                                                               ##STR129##    M.p. 99 to 100° C. (recrystallized from                                isopropyl ether)                                         53-(1)                                                                               ##STR130##    oil; NMR, δ: 1.20-1.84(m, 6H, CH.sub.2),                                2.31(s, 3H, CH.sub.3), 2.49(s, 3H, CH.sub.3)                                  2.68-2.97(m, 4H, NCH.sub.2), 4.53(s, 2H, SCH.sub.2)                           Mass(m/e): 379(M.sup.+ + 1), 173                         54-(1)                                                                               ##STR131##    oil; NMR, δ: 1.30-1.85(m, 6H, CH.sub.2),                                2.50-2.95(m, 4H, NCH.sub.2), 3.96(s, 3H, OCH.sub.3),                          .59(s, 2H, SCH.sub.2) Mass(m/e): 380(M.sup.+), 173       55-(1)                                                                               ##STR132##    oil; NMR, δ: 1.33-1.73(m, 6H, CH.sub.2),                                2.05(s, 3H, CCH.sub.3), 2.70-2.76(m, 4H, NCH.sub.2),                          .43(s, 2H, SCH.sub.2) Mass(m/e): 364(M.sup.+), 173       56-(1)                                                                               ##STR133##    M.p. 123.5 to 125.5° C.  (recrystallized from                          thyl acetate and n-hexane)                               57-(1)                                                                               ##STR134##    oil; NMR, δ: 1.60(br, 6H, CH.sub.2), 2.48(s,                            3H, CCH.sub.3), 2.77-2.88(m, 4H, NCH.sub.2), 3.80(s,                          3H, OCH.sub.3), 4.55(s, 2H, SCH.sub.2) Mass(m/e):                             394(M.sup.+), 173                                        58-(1)                                                                               ##STR135##    M.p. 115 to 117° C. (recrystallized from                               ethyl acetate and n-hexane)                              ______________________________________                                         *note: NMR is measured in CDCl.sub.3                                     

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 8.

                  TABLE 8                                                         ______________________________________                                         ##STR136##                                                                   (wherein n = 0)                                                               Ex.   Compound (I-d)                                                          Nos.  Ring A         Properties*                                              ______________________________________                                        51-(2)                                                                               ##STR137##    M.p. 62 to 64° C. (recrystallized from                                 chloroform and isopropyl ether)                          52-(2)                                                                               ##STR138##    M.p. 108 to 111° C. (recrystallized from                               isopropyl alcohol and isopropyl ether)                   53-(2)                                                                               ##STR139##    M.p. 143 to 145° C. (recrystallized from                               ethyl acetate)                                           54-(2)                                                                               ##STR140##    M.p. 152 to 153° C. (recrystallized from                               ethyl acetate)                                           55-(2)                                                                               ##STR141##    M.p. 94 to 96° C. (recrystallized from ethyl                           acetate and n-hexane)                                    56-(2)                                                                               ##STR142##    oil; NMR, δ: 1.4-1.8(m, 6H, CH.sub.2),                                  2.5-2.9(m, 4H, NCH.sub.2), 3.80(s, 3H, OCH.sub.3),                            4.75(ABq, 2H, SCH.sub.2) FABMass(m/e): 397(M.sup.+ +                          1), 174                                                  57-(2)                                                                               ##STR143##    M.p. 129 to 131° C. (recrystallized from                               ethyl acetate)                                           58-(2)                                                                               ##STR144##    M.p. 94 to 96° C. (recrystallized from ethyl                           acetate and n-hexane)                                    ______________________________________                                         *note: NMR is measured in CDCl.sub.3                                     

EXAMPLES 59 TO 64

(1) The corresponding starting compounds are treated in the same manneras descibed in Example 1-(1) to give the compounds shown in Table 9.

                  TABLE 9                                                         ______________________________________                                         ##STR145##                                                                   Ex.   Compound (II-e)                                                         Nos.  R            Properties*                                                ______________________________________                                        59-(1)                                                                              N(n-C.sub.3 H.sub.7).sub.2                                                                 oil; NMR, δ: 0.79(t, 6H,                                                J=7Hz, CCH.sub.3),                                                            4.61(s, 2H, SCH.sub.2)                                                        Mass(m/e): 367(M.sup.+  + 1), 190                          60-(1)                                                                              CH.sub.2 N(CH.sub.3).sub.2                                                                 M.p. 48 to 52° C. (recrystallized                                      from ethyl acetate and n-hexane)                           61-(1)                                                                               ##STR146##  oil; NMR, δ: 1.0-2.1(m, 10H, CH.sub.2), 3.1-3.5(b                       r, 1H, CHN), 4.44(s, 2H, SCH.sub.2), 4.7-5.0(br, 1H,                          NH) Mass(m/e): 364(M.sup.+), 188                           62-(1)                                                                               ##STR147##  oil; NMR, δ: 4.23(s, 2H, SCH.sub.2) Mass(m/e):                          333(M.sup.+)                                               63-(1)                                                                              H            M.p. 69 to 71° C. (recrystallized                                      from isopropyl ether and n-hexane)                         64-(1)                                                                              OCH.sub.3    M.p. 68 to 70° C. (recrystallized                                      from ether and isopropyl ether)                            ______________________________________                                         *note:                                                                        NMR is measured in CDCl.sub.3                                            

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 10.

                  TABLE 10                                                        ______________________________________                                         ##STR148##                                                                   Ex.   Compound (I-e)                                                          Nos.  R            Properties*                                                ______________________________________                                        59-(2)                                                                              N(n-C.sub.3 H.sub.7).sub.2                                                                 oil; NMR, δ: 0.76(t, 6H, J=7Hz,                                         CH.sub.2 CH.sub.2 CH.sub.3), 4.88(ABq, 2H, SCH.sub.2)                         IRν.sub.max.sup.liquid (cm.sup.-1): 1050 (SO)           60-(2)                                                                              CH.sub.2 N(CH.sub.3).sub.2                                                                 M.p. 96 to 97.5° C.(recrystallized                                     from ethyl acetate and n-hexane)                           61-(2)                                                                               ##STR149##  oil; NMR, δ: 3.05-3.45(m, 1H, CH), 4.65(ABq, 2H,                        SCH.sub.2), 5.30(br, 1H, NH) IRν.sub.max.sup.liquid                        (cm.sup.-1): 3320, 1040                                    62-(2)                                                                               ##STR150##  M.p. 188 to 190°  C.(recrystallized from                               ethanol)                                                   63-(2)                                                                              H            M.p. 151 to 153° C. (recrystallized                                    from ethanol and ether)                                    64-(2)                                                                              OCH.sub.3    M.p. 148 to 151° C. (recrystallized                                    from ethanol)                                              ______________________________________                                         *note:                                                                        NMR is measured in CDCl.sub.3                                            

EXAMPLES 65 TO 66

(1) The corresponding starting compounds are treated in the same manneras described in Example 1-(1) to give the compounds shown in Table 11.

                  TABLE 11                                                        ______________________________________                                         ##STR151##                                                                   Ex.   Compound (II-f)                                                         Nos.  R            Properties*                                                ______________________________________                                        65-(1)                                                                              N(CH.sub.3).sub.2                                                                          oil; NMR, δ: 1.70-1.97(m, 4H, CH.sub.2),                                2.40-2.87(m, 4H, CCH.sub.2),                                                  2.60(s, 6H, N(CH.sub.3).sub.2),                                               4.39(s, 2H, SCH.sub.2)                                                        Mass(m/e): 364(M.sup.+), 134                               66-(1)                                                                               ##STR152##  oil; NMR, δ: 1.76-1.89(m, 4H, CH.sub.2),                                2.43-2.71(m, 4H, CCH.sub.2), 2.73-2.87(m, 4H,                                 N(CH.sub.2), 3.68-3.81 (m, 4H, OCH.sub.2), 4.40(s, 2H,                        SCH.sub.2) Mass(m/e): 406(M.sup.+)                         ______________________________________                                         *note:                                                                        NMR is measured in CDCl.sub.3                                            

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 12.

                  TABLE 12                                                        ______________________________________                                         ##STR153##                                                                   Ex.   Compound (I-f)                                                          Nos.  R            Properties*                                                ______________________________________                                        65-(2)                                                                              N(CH.sub.3).sub.2                                                                          oil; NMR, δ: 2.59(s, 6H, N(CH.sub.3).sub.2),                            4.80(ABq, 2H, SCH.sub.2)                                                      FABMass(m/e): 381(M.sup.+  + 1)                            66-(2)                                                                               ##STR154##  oil; NMR, δ: 4.82(ABq, 2H, SCH.sub.2) FABMass(m/e                       ): 423(M.sup.+  + 1)                                       ______________________________________                                         *note:                                                                        NMR is measured in CDCl.sub.3                                            

EXAMPLE 67

(1) A solution of 7.53 g of2-(2-dimethylaminobenzylthio)-1,3a,4,5,6,6a-hexahydro-6a-hydroxy-1-(2-pyridyl)cyclopenta[d]imidazoleand a catalytic amount of p-toluenesulfonic acid in 100 ml of toluene isrefluxed for 1 hour. The reaction mixture is evaporated to remove thesolvent, water is added to the residue, and the aqueous mixture isneutralized with an aqueous sodium bicarbonate solution. The mixture isextracted with chloroform. The extract is dried and evaporated to removethe solvent, whereby 3.94 g of1,4,5,6-tetrahydro-2-(2-dimethylaminobenzylthio)-1-(2-pyridyl)cyclopenta[d]imidazoleare obtained.

Yield 55%

M.p. 115° to 117° C. (recrystallized from ethyl acetate and n-hexane)

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1,4,5,6-tetrahydro-2-(2-dimethylaminobenzylsulfinyl)-1-(2-pyridyl)cyclopenta[d]imidazole.

Yield 74%

M.p. 139.5° to 141° C. (recrystallized from ethyl acetate and n-hexane)

EXAMPLES 68 TO 70

(1) The corresponding starting compounds are treated in the same manneras described in Example 67-(1) to give the compounds shown in Table 13.

                  TABLE 13                                                        ______________________________________                                         ##STR155##                                                                    ##STR156##                                                                   Ex.   Compound(II-g)                                                          Nos.  R            Properties                                                 ______________________________________                                        68-(1)                                                                              N(C.sub.2 H.sub.5).sub.2                                                                   M.p. 106 to 108° C. (recrystallized                                    from ethyl acetate and n-hexane)                           69-(1)                                                                               ##STR157##  M.p. 120 to 122.5° C. (recrystallized from                             ethyl acetate and n-hexane)                                70-(1)                                                                               ##STR158##  M.p. 115 to 116° C. (recrystallized from                               isopropyl ether)                                           ______________________________________                                    

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 14.

                  TABLE 14                                                        ______________________________________                                         ##STR159##                                                                   Ex.   Compound(I-g)                                                           Nos.  R           Properties                                                  ______________________________________                                        68-(2)                                                                              N(C.sub.2 H.sub.5).sub.2                                                                  M.p. 107 to 109° C. (recrystallized                                    from ethyl acetate and n-hexane)                            69-(2)                                                                               ##STR160## M.p. 147 to 148.5° C. (recrystallized from ethyl                       acetate and n-hexane)                                       70-(2)                                                                               ##STR161## M.p. 135 to 136.5° C. (recrystallized from ethyl                       acetate)                                                    ______________________________________                                    

EXAMPLE 71

(1) 1-(2-pyridyl)-2-mercaptoimidazole and(2,4,6-trimethylphenyl)sulfonylaminobenzyl chloride are treated in thesame manner as described in Example 1-(1) to give1-(2-pyridyl)-2-[2-(2,4,6-trimethylphenyl)sulfonylaminobenzylthio]imidazole.

Yield 87%

M.p. 154° to 156° C. (recrystallized from isopropyl alcohol)

(2) A mixture of 2 g of the product obtained above, 2.5 ml of anisoleand 15 ml of methanesulfonic acid is stirred at room temperature for 20hours. After the reaction, the mixture is added to water and extractedwith ethyl acetate. The extract is washed with a saturated aqueoussodium chloride solution, dried and evaporated to remove the solvent,whereby 1.1 g of 1-(2-pyridyl)-2-(2-aminobenzylthio)imidazole areobtained as an oil.

Yield 93%

Mass(m/e): 282(M⁺), 106

¹ H-NMR(CDCl₃,δ): 3.9(br,2H,NH₂),4.43(s,2H,SCH₂)

(3) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(2-pyridyl)-2-(2-aminobenzylsulfinyl)imidazole.

M.p. 145° to 146° C. (recrystallized from isopropyl alcohol)

EXAMPLE 72

(1) A mixture of 4.8 g of 1-(2-pyridyl)-2-(2-aminobenzylthio)imidazole,5 ml of acetic acid anhydride and 50 ml of pyridine is stirred at roomtemperature for 16 hours. The solvent is distilled off, and the residueis crystallized with toluene and collected by filtration, whereby 4.31 gof 1-(2-pyridyl)-2-(2-acetylaminobenzylthio)imidazole are obtained.

Yield 78%

M.p. 150° to 151° C. (recrystallized from isopropyl alcohol)

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(2-pyridyl)-2-(2-acetylaminobenzylsulfinyl)imidazole.

M.p. 172° to 173° C. (recrystallized from isopropyl alcohol)

EXAMPLE 73

(1) 100 mg of 60% sodium hydride are suspended in 2 ml of dimethylformamide, and a solution of one g of1-(2-pyridyl)-2-[2-(2,4,6-trimethylphenyl)sulfonylaminobenzylthio]imidazolein 2 ml of dimethyl formamide is added thereto under ice-cooling. Themixture is stirred at room temperature for 30 minutes, and 320 mg ofmethyl iodide are added thereto. The mixture is stirred for 2 hours. Thereaction mixture is poured into water, and the resultant oily product isextracted with ethyl acetate. The extract is dried and evaporated. Theresidue is purified by silica gel column chromatography (solvent;n-hexane:ethyl acetate=3:2), whereby 0.76 g of1-(2-pyridyl)-2-{2-[N-methyl-N-(2,4,6-trimethylphenyl)sulfonylamino]benzylthio}imidazoleis obtained.

M.p. 131° to 133° C. (recrystallized from ethyl acetate)

(2) The product obtained above is treated in the same manner asdescribed in Example 71-(2) to give1-(2-pyridyl)-2-(2-methylaminobenzylthio)imidazole as an oil.

Yield 92%

Mass(m/e): 296(M⁺), 120

¹ H-NMR(CDCl₃,δ): 2.83(d,3H,J=3Hz,NCH₃),4.42(s,2H,SCH₂), 5.20(br,1H,NH)

(3) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(2-pyridyl)-2-(2-methylaminobenzylsulfinyl)imidazole.

M.p. 135° to 137° C. (recrystallized from ethyl acetate)

EXAMPLE 74

(1) 1-(2-pyridyl)-2-(2-acetylaminobenzylthio)imidazole is treated in thesame manner as described in Example 73-(1) to give1-(2-pyridyl)-2-[2-(N-methyl-N-acetylamino)benzylthio]imidazole as anoil.

Yield 78%

Mass(m/e): 338(M⁺), 120

¹ H-NMR(CDCl₃,δ): 1.76(s,3H,COCH₃,3.20(s,3H,NCH₃), 4.39(s,2H,SCH₂)

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(2-pyridyl)-2-[2-(N-methyl-N-acetylamino)benzylsulfinyl]imidazole.

M.p. 188° to 189° C. (recrystallized from chloroform and isopropylethyl)

EXAMPLE 75

(1)2-(2-phthalimidobenzylthio)-1,3a,4,5,6,6a-hexahydro-6a-hydroxy-1-(2-pyridyl)cyclopenta[d]imidazoleis treated in the same manner as described in Example 67-(1) to give1,4,5,6-tetrahydro-1-(2-pyridyl)-2-(phthalimidobenzylthio)cyclopenta[d]imidazole.

M.p. 196° to 197° C. (recrystallized from chloroform and ethyl acetate)

(2) A mixture of 1.80 g of the product obtained above, 0.22 g ofhydrazine hydrate and 100 ml of methanol is refluxed for 5 hours. Afterthe reaction mixture is cooled, the solvent is distilled off, andmethylene chloride is added to the residue. Insoluble materials arefiltered off. The filtrate is washed with water, dried and evaporated toremove the solvent. The crystalline residue is recrystallized from amixture of ethyl acetate and n-hexane, whereby 1.06 g of1,4,5,6-tetrahydro-1-(2-pyridyl)-2-(2-aminobenzylthio)cyclopenta[d]imidazoleare obtained as pale yellow plates.

Yield 83%

M.p. 121° to 123° C.

(3) A solution of 0.27 g of acetyl chloride in 5 ml of methylenechloride is added dropwise to 20 ml of methylene chloride containing 1.0g of the product obtained above and 0.35 g of triethylamine. Saiddropwise addition is carried out under ice-cooling. After 1 hour, thereaction mixture is washed with a saturated aqueous sodium bicarbonatesolution and water, dried and evaporated to remove the solvent. Thecrystalline residue is recrystallized from a mixture of chloroform andethyl acetate, whereby 0.83 g of1,4,5,6-tetrahydro-1-(2-pyridyl)-2-(acetylaminobenzylthio)cyclopenta[d]imidazoleis obtained.

Yield 74%

M.p. 214 to 217 (decomp.)

(4) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1,4,5,6-tetrahydro-1-(2-pyridyl)-2(acetylaminobenzylsulfinyl)cyclopenta[d]imidazole.

M.p. 188° to 191° C. (decomp., recrystallized from ethyl acetate andn-hexane)

EXAMPLE 76

(1) 1-(4-pyridyl)-2-mercaptoimidazole and 2-phthalimidobenzyl chlorideare treated in the same manner as described in Example 1-(1) to give1-(4-pyridyl)-2-(2-phthalimidobenzylthio)imidazole.

M.p. 145° to 147° C. (recrystallized from ethanol)

(2) The product obtained above is treated in the same manner asdescribed in Example 75-(2) to give1-(4-pyridyl)-2-(2-aminobenzylthio)imidazole as an oil.

Mass(m/e): 282(M⁺), 106

¹ H-NMR(CDCl₃,δ): 4.21(br,2H,NH₂),4.30(s,2H,SCH₂),

(3) The product obtained above is treated in the same manner asdescribed in Example 75-(3) to give1-(4-pyridyl)-2-(2-acetylaminobenzylthio)imidazole.

M.p. 153° to 155° C. (recrystallized from ethyl acetate and n-hexane)

(4) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(4-pyridyl)-2-(2-acetylaminobenzylsulfinyl)imidazole.

M.p. 147° to 149° C. (recrystallized from isopropyl alcohol andisopropyl ether)

EXAMPLE 77

(1) 1-(2-pyridylmethyl)-2-mercaptoimidazole and 2-phthalimidobenzylchloride are treated in the same manner as described in Example 1-(1) togive 1-(2-pyridylmethyl)-2-(2-phthalimidobenzylthio)imidazole.

M.p. 80° to 83° C. (recrystallized from ethanol)

(2) The product obtained above is treated in the same manner asdescribed in Example 75-(2) to give1-(2-pyridylmethyl)-2-(2-aminobenzylthio)imidazole as an oil.

Mass(m/e): 296(M⁺), 106

¹ H-NMR(CDCl₃,δ): 4.21(s,2H,SCH₂),4.31(br,2H,NH₂),

5.10(s,2H,NCH₂)

(3) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(2-pyridylmethyl)-2-(2-aminobenzylsulfinyl)imidazole.

Mass(m/e): 312(M⁺), 106

¹ H-NMR(CDCl₃,δ): 4.26(br,2H,NH₂),4.59(ABq,2H,NCH₂),

5.29(ABq,2H,NCH₂)

EXAMPLE 78

(1) A solution containing n-butyl lithium (15%) in 14.3 ml of a n-hexaneare added at -60° C. to 50 ml of tetrahydrofuran containing 4.33 g ofo-(N-methyl-N-phenylamino)benzylalcohol. After 20 minutes, 2.67 g oftriethylamine are added to the mixture, and a solution of 5.03 g ofp-toluenesulfonyl chloride in 20 ml of tetrahydrofuran is added dropwisethereto. The mixture is stirred at -20° C. for 1 hour. 5.0 g oftriethylamine and 3.59 g of 1-(2-pyridyl)-2-mercaptoimidazole arefurther added thereto. After 2 hours, ethyl acetate is added to thereaction mixture. Then, the mixture is washed with water, dried andevaporated to remove the solvent. The residue is purified by columnchromatography (solvent; ethyl acetate:chloroform=1:9), whereby 4.55 gof 1-(2-pyridyl)-2-(N-methyl-N-phenylaminobenzylthio)imidazole areobtained.

Yield 60%

M.p. 90° to 92° C. (recrystallized from ethyl acetate and n-hexane)

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(2-pyridyl)-2-(N-methyl-N-phenylaminobenzylsulfinyl)imidazole.

M.p. 137° to 139° C. (recrystallized from isopropyl alcohol andn-hexane)

EXAMPLES 79 TO 84

(1) The corresponding starting compounds are treated in the same manneras described in Example 78-(1) to give the compounds shown in Table 15.

                  TABLE 15                                                        ______________________________________                                         ##STR162##                                                                    ##STR163##                                                                   Ex.   Compound(II-h)                                                          Nos.  Ring A        Properties*                                               ______________________________________                                        79-(1)                                                                               ##STR164##   oil; NMR, δ :3.96(s, 3H, OCH.sub.3), 4.33(s,                            2H, SCH.sub.2), 6.27(t, 2H, CH)Mass(m/e):362(M.sup.+)                         N                                                         80-(1)                                                                               ##STR165##   oil; NMR, δ :2.38(s, 3H, CCH.sub.3),  4.26(s,                           2H, SCH.sub.2), 6.25(t, 2H, CH)6.81(t, 2H, NCH)                               Mass(m/e):349(M.sup.+), 192                               81-(1)                                                                               ##STR166##   oil; NMR, δ :2.03(s, 3H, CCH.sub.3), 4.11(s,                            2H, SCH.sub.2), 6.23(t, 2H, CH )6.71(t, 2H, NCH)                              Mass(m/e):346(M.sup.+), 192                               82-(1)                                                                               ##STR167##   oil; NMR, δ :3.79(s, 3H, OCH.sub.3), 4.38(s,                            2H, SCH.sub.2), 6.24(t, 2H, CH)6.72(t, 2H, NCH)                               Mass(m/e):362(M.sup.+), 208                               83-(1)                                                                               ##STR168##   oil                                                       84-(1)                                                                               ##STR169##                                                                                  ##STR170##                                               ______________________________________                                         *note: NMR is measured in CDCl.sub.3                                     

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 16.

                  TABLE 16                                                        ______________________________________                                         ##STR171##                                                                   Ex.   Compound(I-h)                                                           Nos.  Ring A        Properties*                                               ______________________________________                                        79-(2)                                                                               ##STR172##   M.p. 112 to 114° C. (recrystallized from ethyl                         acetate and n-hexane)                                     80-(2)                                                                               ##STR173##   M.p. 106 to 120° C. (recrystallized from                               chloroform and n-hexane)                                  81-(2)                                                                               ##STR174##   M.p. 113 to 115° C. (recrystallized from ethyl                         acetate and n-hexane)                                     82-(2)                                                                               ##STR175##                                                                                  ##STR176##                                               83-(2)                                                                               ##STR177##   M.p. 127 to 128.5° C. (recrystallized) from                            ethyl acetate and n-hexane)                               84-(2)                                                                               ##STR178##   M.p. 116 to 118° C. (recrystallized from ethyl                         acetate and n-hexane)                                     ______________________________________                                         *note: NMR is measured in CDCl.sub.3                                     

EXAMPLE 85

(1) 19.6 g of1-(5-nitro-2-pyridyl)-2-[2-(dimethylamino)benzylthio]imidazole aredissolved in 400 ml of the mixture of conc. hydrochloric acid and a 70%aqueous ethanol (1:5). A solution of 82.7 g of tin (II) chloridedihydrate in 100 ml of water is added dropwise thereto at 80° C., andthe mixture is stirred for 1 hour at the same temperature. The reactionmixture is made alkaline with an aqueous sodium hydroxide solution, andinsoluble materials are filtered off. The filtrate is extracted withethyl acetate, dried and evaporated to remove the solvent. The residueis purified by silica gel column chromatography (solvent;chloroform:methanol=30:1), and crystallized with ether. The crystals arecollected by filtation, whereby 6.27 g of1-(5-amino-2-pyridyl)-2-[2-(dimethylamino)benzylthio]imidazole areobtained.

M.p. 134° to 138° C.

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(5-amino-2-pyridyl)-2-[2-(dimethylamino)benzylsulfinyl]imidazole.

M.p. 140° to 143° C. (recrystallized from ethanol and ether)

EXAMPLE 86

(1) 1-(5-nitro-2-pyridyl)-2-mercaptoimidazole and 2-morpholinobenzylchloride are treated in the same manner as described in Example 1-(1) togive 1-(5-nitro-2-pyridyl)-2-(2-morpholinobenzylthio)imidazole.

M.p. 199° to 202° C. (recrystallized from chloroform and n-hexane)

(2) 7.95 g of the product obtained above are dissolved in 120 ml ofacetic acid, and subjected to catalytic hydrogenation in the presence of2.5 g of 10% palladium-carbon at room temperature under atmosphericpressure. After the reaction, the catalyst is filtered off, and thefiltrate is evaporated to remove the solvent. Water is added to theresidue, and the aqueous mixture is neutralized with a saturated aqueoussodium bicarbonate solution. The crystalline precipitates are collectedby filtration, and recrystallized from chloroform and n-hexane, whereby5.92 g of 1-(5-amino-2-pyridyl)-2-(2-morpholinobenzylthio)imidazole areobtained.

Yield 81%

M.p. 178° to 181° C.

(3) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(5-amino-2-pyridyl)-2-(2-morpholinobenzylsulfinyl)imidazole.

M.p. 190° to 192° C. (decomp. recrystallized from chloroform andn-hexane)

EXAMPLE 87

(1) 1-(5-amino-2-pyridyl)-2-(2-morpholinobenzylthio)imidazole is treatedin the same manner as described in Example 75-(3) to give1-(5-acetylamino-2-pyridyl)-2-(2-morpholinobenzylthio)imidazole.

Yield 78%

M.p. 164° to 167° C. (recrystallized from chloroform and n-hexane)

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(5-acetylamino-2-pyridyl)-2-(2-morpholinobenzylsulfinyl)imidazole.

M.p. 207° to 209° C. (decomp. recrystallized from chloroform andn-hexane)

EXAMPLES 88 TO 91

(1) The corresponding starting compounds are treated in the same manneras described in Example 1-(1) to give the compounds shown in Table 17.

                  TABLE 17                                                        ______________________________________                                         ##STR179##                                                                    ##STR180##                                                                   Ex.   Compound (II-i)                                                         Nos.  Ring A         Properties                                               ______________________________________                                        88-(1)                                                                               ##STR181##    M.p. 106 to 107° C.(recrystallized from ethyl                          acetate)                                                 89-(1)                                                                               ##STR182##    M.p. 96 to 98° C.(recrystallized from ethyl                            acetate and n-hexane)                                    90-(1)                                                                               ##STR183##    M.p. 112 to 118° C.(recrystallized from ethyl                          acetate and n-hexane)                                    91-(1)                                                                               ##STR184##    M.p. 118 to 119° C.(recrystallized from                                ethanol and isopropyl ether)                             ______________________________________                                    

(2) The products obtained above are treated in the same manner asdescribed in Example 86-(2) to give the compounds shown in Table 18.

                  TABLE 18                                                        ______________________________________                                         ##STR185##                                                                   Ex.   Compound (II-j)                                                         Nos.  Ring A         Properties*                                              ______________________________________                                        88-(2)                                                                               ##STR186##    M.p. 116 to 118° C.(recrystallized from ethyl                          acetate and n-hexane)                                    89-(2)                                                                               ##STR187##    M.p. 93 to 95° C.(recrystallized from ethyl                            acetate and n-hexane)                                    90-(2)                                                                               ##STR188##    M.p. 112 to 118° C.(recrystallized from ethyl                          acetate and n-hexane)                                    91-(2)                                                                               ##STR189##    oil; NMR δ : 3.82(s, 3H, OCH.sub.3, 4.31(s,                             2H, SCH.sub.2), 4.40(br, 2H,  NH.sub.2) Mass(m/e):                            312(M.sup.+), 106                                        ______________________________________                                         *note: NMR is measured in CDCl.sub.3                                     

(3) The products obtained above are treated in the same manner asdescribed in Example 75-(3) to give the compounds shown in Table 19.

                  TABLE 19                                                        ______________________________________                                         ##STR190##                                                                   Ex.   Compound (II-k)                                                         Nos.  Ring A         Properties                                               ______________________________________                                        88-(3)                                                                               ##STR191##    M.p. 173 to 175° C.(recrystallized from                                isopropyl alcohol and isopropyl ether)                   89-(3)                                                                               ##STR192##    M.p. 131 to 133° C.(recrystallized from ethyl                          acetate and n-hexane)                                    90-(3)                                                                               ##STR193##    M.p. 137 to 140.5° C.(recrystallized from                              ethyl acetate and n-hexane)                              91-(3)                                                                               ##STR194##     M.p. 147 to 149° C.(recrystallized from                               ethyl acetate)                                           ______________________________________                                    

(4) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 20.

                  TABLE 20                                                        ______________________________________                                         ##STR195##                                                                   Ex.   Compound (I-i)                                                          Nos.  Ring A         Properties                                               ______________________________________                                        88-(4)                                                                               ##STR196##    M.p. 192 to 194° C.(recrystallized from                                methylene chloride and n-hexane)                         89-(4)                                                                               ##STR197##    M.p. 185 to 193° C.(recrystallized from                                methylene chloride and n-hexane)                         90-(4)                                                                               ##STR198##    M.p. 155.5 to 157.5° C.(recrystal- lized from                          methylene chloride and n-hexane)                         91-(4)                                                                               ##STR199##    M.p. 110 to 113° C.(recrystallized from ethyl                          acetate)                                                 ______________________________________                                    

EXAMPLE 92

(1) 1-(2-pyridylmethyl)-2-(2-aminobenzylthio)imidazole is treated in thesame manner as described in Example 75-(3) to give1-(2-pyridylmethyl)-2-(2-acetylaminobenzylthio)imidazole.

Mass (m/e): 338(M⁺), 106

¹ H-NMR(CDCl₃,δ): 2.29(s,3H,COCH₃), 4.31(s,2H,SCH₂),5.10(s,2H,NCH₂)

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(2-pyridylmethyl)-2-(2-acetylaminobenzylsulfinyl)imidazole.

M.p. 146° to 148° C. (recrystallized from ethyl acetate and n-hexane)

EXAMPLE 93

(1) 0.26 ml of acetyl chloride is added to a mixture of 0.98 g of1-(5-amino-2-pyridyl)-2-[2-(dimethylamino)benzylthio]imidazole, 1 ml oftriethylamine and 30 ml of methylene chloride under ice-cooling. Themixture is stirred at the same temperature for 2 hours, washed withwater and a saturated aqueous sodium bicarbonate solution, dried andevaporated to remove the solvent. The residue is purified by silica gelcolumn chromatography (solvent; chloroform:methanol=30:1), andcrystallized with isopropyl ether. The crystals are collected byfiltration, whereby 0.82 g of1-(5-acetylamino-2-pyridyl)-2-[2-(dimethylamino)benzylthio]imidazole isobtained.

M.p. 137° to 139° C.

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(5-acetylamino-2-pyridyl)-2-[2-(dimethylamino)benzylsulfinyl]imidazole.

M.p. 168° to 170° C. (recrystallized from ethanol and ether)

EXAMPLE 94

(1) 1.4 g of acetic acid anhydride are added to 2.5 ml of formic acid,and the mixture is stirred at 60° C. for 30 minutes. The reactionsolution is cooled in an ice bath, a solution of 1.07 g of1-(4,6-dimethyl-2-pyridyl)-2-(2-aminobenzylthio)imidazole in 4 ml offormic acid is added thereto, and the mixture is stirred at roomtemperature for 1 hour. After the reaction, the solvent is distilledoff. Water is added to the residue, and the aqueous mixture is madealkaline with potassium carbonate. The mixture is then extracted withethyl acetate, dried and evaporated to remove the solvent. The residueis purified by silica gel column chromatography (solvent; ethylacetate:n-hexane=1:1). The crude crystals obtained above arerecrystallized from a mixture of ethyl acetate and n-hexane, whereby0.64 g of1-(4,6-dimethyl-2-pyridyl)-2-(2-formylaminobenzylthio)imidazole isobtained.

Yield 55%

M.p. 124° to 126.5° C.

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(4,6-dimethyl-2-pyridyl)-2-(2-formylaminobenzylsulfinyl)imidazole.

M.p. 160° to 162° C. (decomp. recrystallized from methylene chloride andn-hexane)

EXAMPLE 95

(1) A solution of 1.7 g of potassium carbonate in 10 ml of water isadded to 10 ml of methylene chloride containing 1.2 g of1-(2-pyridyl)-2-(2-aminobenzylthio)imidazole. 0.65 g of benzoyl chlorideis added thereto under vigourous stirring, the mixture is stirred atroom temperature for 1 hour. After the reaction, the organic layer isseparated therefrom, washed with water, dried and evaporated to removethe solvent. The crude crystals obtained above are recrystallized from amixture of isopropyl alcohol and isopropyl ether, whereby 1.55 g of1-(2-pyridyl)-2-(2-benzoylaminobenzylthio)imidazole are obtained.

Yield 95%

M.p. 132° to 133° C.

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(2-pyridyl)-2-(2-benzoylaminobenzylsulfinyl)imidazole.

M.p. 109° to 111° C. (recrystallized from ethyl acetate)

EXAMPLES 96 TO 97

(1) The corresponding starting compounds are treated in the same manneras described in Example 95-(1) to give the compounds shown in Table 21.

                  TABLE 21                                                        ______________________________________                                         ##STR200##                                                                    ##STR201##                                                                   Ex.    Compound(II-1)                                                         Nos.   R            Properties                                                ______________________________________                                        96-(1) NHCO.sub.2 C.sub.2 H.sub.5                                                                 M.p. 119 to 120° C. (recrystallized                                    from isopropyl alcohol and                                                    isopropyl ether)                                          97-(1) NHCOC.sub.2 H.sub.5                                                                        M.p. 98 to 100° C. (recrystallized                                     from isopropyl alcohol and                                                    isopropyl ether)                                          ______________________________________                                    

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 22.

                  TABLE 22                                                        ______________________________________                                         ##STR202##                                                                                                 (I-j)                                           Ex.   Compound(I-j)                                                           Nos.  R            Properties                                                 ______________________________________                                        96-(2)                                                                              NHCO.sub.2 C.sub.2 H.sub.5                                                                 M.p. 109 to 112° C. (recrystallized                                    from ethyl acetate)                                        97-(2)                                                                              NHCOC.sub.2 H.sub.5                                                                        M.p. 155 to 156° C. (recrystallized                                    from chloroform and isopropyl ether)                       ______________________________________                                    

EXAMPLE 98

(1) 0.96 ml of acetyl chloride is added dropwise to 100 ml of methylenechloride containing 2.94 g of1-(3-hydroxy-2-pyridyl)-2-(2-dimethylaminobenzylthio)imidazole and 3.76ml of triethylamine. Said dropwise addition is carried out in underice-cooling. After 2 hour, the reaction mixture is washed with water,dried and evaporated to remove the solvent. The residue is purified bysilica gel column chromatography (solvent; chloroform:acetone=30:1), andrecrystallized from a mixture of ethyl acetate and n-hexane, whereby2.08 g of 1-(3-acetoxy-2-pyridyl)-2-(2-dimethylaminobenzylthio)imidazoleare obtained as colorless needles.

Yield 63%

M.p. 85° to 87° C.

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(3-acetoxy-2-pyridyl)-2-(2-dimethylaminobenzylsulfinyl)imidazole isobtained as an oil.

FABMass(m/e): 385 (M⁺ +1), 134

¹ H-NMR(CDCl₃, δ): 2.19 (s, 3H, COCH₃), 2.57 (s, 6H, N(CH₃)₂), 4.77(ABq, 2H, SCH₂)

IR ν_(max) ^(Nujol) (cm⁻¹): 1770 (NHCO), 1045 (S-O).

EXAMPLE 99

(1) 1-(3-hydroxy-2-pyridyl)-2-(2-morpholinobenzylthio)imidazole istreated in the same manner as described in Example 98-(1) to give1-(3-acetoxy-2-pyridyl)-2-(2-morpholinobenzylthio)imidazole.

Yield 73%

M.p. 89° to 91° C. (recrystallized from ethyl acetate and n-hexane).

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(3-acetoxy-2-pyridyl)-2-(2-morpholinobenzylsulfinyl)imidazole.

M.p. 104° to 107° C. (recrystallized from ethyl acetate and n-hexane).

EXAMPLE 100

(1) 0.48 g of methanesulfonyl chloride is added to 10 ml of methylenechloride containing 1.09 g of1-(4,6-dimethyl-2-pyridyl)-2-(2-aminobenzylthio)imidazole and 0.5 ml oftriethylamine. Said dropwise addition is carried out under ice-cooling.After 1 hour, the reaction mixture is washed with water, dried andevaporated to remove the solvent. The residue is purified by silica gelcolumn chromatography (solvent; chloroform:ethyl acetate=10:1), andrecrystallized from a mixture of ethyl acetate and n-hexane, whereby 1.0g of1-(4,6-dimethyl-2-pyridyl)-2-(2-methanesulfonylaminobenzylthio)imidazoleas colorless needles.

Yield 73%

M.p. 121° to 123° C.

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(4,6-dimethyl-2-pyridyl)-2-(2-methanesulfonylaminobenzylsulfinyl)imidazole.

138° to 142° C. (recrystallized from methylene chloride and n-hexane).

EXAMPLE 101

(1) 3.26 g of1-(3-hydroxy-2-pyridyl)-2-(2-dimethylaminobenzylthio)imidazole aredissolved in 100 ml of dimethyl formamide, and 0.48 g of 60% sodiumhydride is added thereto. After the mixture is stirred for 20 minutes,1.3 ml of isopropyl bromide are added dropwised thereto, and the mixtureis further stirred at room temperature for 17 hours. The reactionmixture is poured into ice water, extracted with ethyl acetate, driedand evaporated to remove the solvent. The residue is recrystallized froma mixture of ethyl acetate and n-hexane, whereby 2.47 g of1-(3-isopropoxy-2-pyridyl)-2-(2-dimethylaminobenzylthio)imidazole areobtained.

Yield 67%

M.p. 85° to 87° C.

(2) The product obtained above is treated in the same manner asdescribed in Example 1-(2) to give1-(3-isopropoxy-2-pyridyl)-2-(2-dimethylaminobenzylsulfinyl)imidazole.

Mass(m/e): 384 (M⁺), 134

¹ H-NMR(CDCl₃, δ): 1.32 and 1.34 (d, 3H, CH₃, respectively), 2.63 (s,6H, N(CH₃)₂), 4.81 (ABq, 2H, SCH₂).

EXAMPLES 102 TO 103

(1) The corresponding starting compounds are treated in the same manneras described in Example 101-(1) to give the compounds shown in Table 23.

                  TABLE 23                                                        ______________________________________                                         ##STR203##                  (II-o)                                           Ex.    Compound(II-o)                                                         Nos.   Ring A          Properties                                             ______________________________________                                        102-(1)                                                                               ##STR204##     M.p. 117 to 119° C. (recrystallized from                               ethyl acetate and n-hexane)                            103-(1)                                                                               ##STR205##     M.p. 87 to 89° C. (recrystallized from                                 ethyl acetate and n-hexane)                            ______________________________________                                    

(2) The products obtained above are treated in the same manner asdescribed in Example 1-(2) to give the compounds shown in Table 24.

                  TABLE 24                                                        ______________________________________                                         ##STR206##                   (I-k)                                           Ex.   Compound(I-k)                                                           Nos.  Ring A          Properties*                                             ______________________________________                                        102-(2)                                                                              ##STR207##     M.p. 120 to 122° C. (recrystallized from                               ethyl acetate and n-hexane)                             103-(2)                                                                              ##STR208##                                                                                    ##STR209##                                             ______________________________________                                         *note: NMR is measured in CDCl.sub.3                                     

EXAMPLE 104

3.42 g of 80% m-chloroperbenzoic acid are added to 100 ml of chloroformcontaining 1.5 g of 1-(4-pyridyl)-(2-dimethylaminobenzylthio)imidazole.Said addition is carried out under ice-cooling. After the mixture isstirred for 1 hour, 8.36 g of sodium hydrosulfite are added thereto, andallowed to stand at room temperature, for 2 hours. The reaction mixtureis washed with a saturated aqueous sodium bicarbonate solution andwater, dried and evaporated to remove the solvent. The residue ispurified by silica gel column chromatography (solvent;chloroform:methanol=40:1), and recrystallized from a mixture ofchloroform and isopropyl ether, whereby 0.91 g of1-(4-pyridyl)-2-(2-dimethylaminobenzylsulfonyl)imidazole is obtained.

M.p. 132° to 135° C.

EXAMPLE 105

(1) 1.76 g of 60% sodium hydride are suspended in 80 ml ofdimethylformamide, and 8.0 g of1-(3-methyl-2-pyridyl)-2-mercaptoimidazole are added thereto underice-cooling. The mixture is stirred at room temperature for 30 minutes,and 13.22 g of o-phthalimidobenzyl bromide are added thereto. Themixture is stirred for 2 hours. After the reaction, the solvent isdistilled off under reduced pressure, and water is added to the residue.The mixture is extracted with ethyl acetate and the extract is washedwith 10% aqueous sodium hydroxide solution and water, dried andevaporated to remove the solvent. The crystalline residue isrecrystallized from a mixture of ethyl acetate and ether, whereby 11.3 gof 1-(3-methyl-2-pyridyl)-2-(2-phthalimidobenzylthio)imidazole areobtained.

Yield 63%

M.p. 135° to 138° C.

(2) 7.05 g of the product obtained above are treated in the same manneras described in Example 75-(2) to give 4.05 g of1-(3-methyl-2-pyridyl)-2-(2-aminobenzylthio)imidazole as an oil.

Mass(m/e): 296 (M⁺), 106

¹ H-NMR(CDCl₃, δ): 2.07 (s, 3H), 4.27 (s, 2H), 4.05-4.5 (br band, D₂ Oexchange, 2H).

(3) 3.5 g of the product obtained above are treated in the same manneras described in Example 1-(2) to give 1.82 g of1-(3-methyl-2-pyridyl)-2-(2-aminobenzylsulfinyl)imidazole.

M.p. 112.5° to 113.5° C. (recrystallized from ethyl acetate).

EXAMPLES 106 TO 107

The corresponding starting compounds are treated in the same manner asdescribed in Example 105 to give the compounds shown in table 27.

                  TABLE 27                                                        ______________________________________                                         ##STR210##                                                                    ##STR211##                                                                   (Wherein n = 0)                                                               Ex.     Compound (I-1)                                                        Nos.    Ring A         Properties                                             ______________________________________                                        106                                                                                    ##STR212##    M.p. 153 to 156° C. (recrystallized from                               ethyl acetate)                                         107                                                                                    ##STR213##    M.p. 158 to 160° C. (recrystallized from                               chloroform and ethyl acetate)                          ______________________________________                                    

EXAMPLE 108

(1) 1.25 g of 1-(4-methyl-2-pyridyl)-2-mercaptoimidazole ando-(2,4,6-trimethylphenyl)sulfonylaminobenzyl chloride are treated in thesame manner as described in Example 1-(1) to give 2.19 g of1-(4-methyl-2-pyridyl)-2-(2-(2,4,6-trimethylphenyl)sulfonylaminobenzylthio)imidazole.

(2) The product obtained above is treated in the same manner asdescribed in Example 73 to give1-(4-methyl-2-pyridyl)-2-(2-methylaminobenzylsulfinyl)imidazole.

M.p. 112.5° to 113.5° C. (recrystallized from ethyl acetate).

EXAMPLES 109 TO 110

The corresponding starting compounds are treated in the same manner asdescribed in Example 108 to give the compounds shown in table 28.

                  TABLE 28                                                        ______________________________________                                         ##STR214##                                                                    ##STR215##                                                                   (Wherein n = 0)                                                               Ex.  Compound (I-m)                                                           Nos. Ring A       R.sup.2     Properties*                                     ______________________________________                                        109                                                                                 ##STR216##  NHCH.sub.2 CH.sub.3                                                                       M.p. 119 to 121° C. (recrystallized                                    from ethyl acetate and ether)                   110                                                                                 ##STR217##  NHCH.sub.3  NMR, δ: 2.17(s, 3H), 2.74(s, 3H)                                        4.66(ABq, 2H), 5.15(br, 1H, D.sub.2 O                                         exchange) CIMass(m/e): 327(M.sup.+ +1),138      ______________________________________                                         *note: NMR is measure in CDCl.sub.3                                      

EXAMPLE 111

(1) 0.77 g of1,4,5,6-tetrahydro-1-(3-methoxy-2-pyridyl)-2-mercaptocyclopenta(d)imidazoleare treated in the same manner as described in Example 1 to give 0.78 gof1,4,5,6-tetrahydro-1-(3-methoxy-2-pyridyl)-2-(2-(dimethylamino)benzylsulfinyl)cyclopenta(d)imidazole.

FABMass(m/e): 397 (M⁺ +1), 134

¹ H-NMR(CDCl₃, δ): 2.60 (s, 6H), 2.45-2.91 (m, 6H), 3.77 (s, 3H), 4.79(ABq, 2H, J=12.3 Hz).

EXAMPLE 112

1.70 g of1,4,5,6-tetrahydro-1-(3-methyl-2-pyridyl)-2-mercaptocyclopenta(d)imidazoleare treaed in the same manner as described in Example 1 to give 1.78 gof1,4,5,6-tetrahydro-1-(3-methyl-2-pyridyl)-2-(2-(dimethylamino)benzylsulfinyl)cyclopenta(d)imidazole.

M.p. 119° to 120° C. (recrystallized from ethyl acetate and n-hexane).

EXAMPLE 113

1-(4-Methyl-2-pyridyl)-2-mercapto imidazole is treaed in the same manneras described in Example 1 to give1-(4-methyl-2-pyridyl)-2-(2-(dimethylamino)benzylsulfinyl)imidazole.

Yield 64%

M.p. 127° to 129° C. (recrystallized from ethyl acetate).

PREPARATION 1

(1) A solution of 3.76 g of 2-aminopyridine and 7 g of 2,2-diethoxyethylisothiocyanate in toluene is refluxed. After the reaction, the solventis distilled off, and the residue is recrystallized from a mixture ofethyl acetate and n-hexane, whereby 9 g ofN-(2,2-diethoxyethyl)-N'-(2-pyridyl)thiourea are obtained.

M.p. 126° to 128° C.

(2) A solution of 8.94 g of the product obtained above and a smallamount of conc. hydrochloric acid in acetic acid is refluxed. After thereaction, the solution is evaporated to remove the solvent. The residueis dissolved in water, and sodium bicarbonate is added thereto. Thecrystalline precipitates are collected by filtration, whereby 4.91 g of1-(2-pyridyl)-2-mercaptoimidazole are obtained.

M.p. 159° to 161° C. (recrystallized from isopropyl alcohol, isopropylether and n-hexane).

PREPARATIONS 2 TO 25

The corresponding starting compounds are treated in the same manner asdescribed in Preparation 1-(1) and (2) to give the compounds shown inTable 25.

                  TABLE 25                                                        ______________________________________                                         ##STR218##                                                                    ##STR219##                                                                   (wherein n = 1 in Pr. No. 2, n = 0 in Pr. Nos. 3 to 24, and n = 2             in Pr. No. 25, R.sup.1 and R.sup.2 are hydrogen atom, R.sup.3 is ethyl,       and                                                                           Z is sulfur atom)                                                             Pr.  Compound (III)                                                           Nos. Ring A           Properties                                              ______________________________________                                         2                                                                                  ##STR220##      M.p. 181 to 183° C. (recrystallized from                               ethanol)                                                 3                                                                                  ##STR221##      M.p. 209.5 to 211.5° C. (recrystallized from                           methanol)                                                4                                                                                  ##STR222##      M.p. 267 to 269° C. (recrystallized from                               ethanol)                                                 5                                                                                  ##STR223##      M.p. 170 to 172° C. (recrystallized from                               methanol)                                                6                                                                                  ##STR224##      M.p. 223 to 225° C. (recrystallized from                               ethanol)                                                 7                                                                                  ##STR225##      M.p. 187 to 190° C. (recrystallized from                               ethanol)                                                 8                                                                                  ##STR226##      M.p. 227 to 229° C. (recrystallized from                               ethanol)                                                 9                                                                                  ##STR227##      M.p. 188 to 190° C. (recrystallized from                               ethanol)                                                10                                                                                  ##STR228##      M.p. 166 to 168° C. (recrystallized from                               ethanol)                                                11                                                                                  ##STR229##      M.p. 222 to 225° C. (recrystallized from                               ethanol)                                                12                                                                                  ##STR230##      M.p. 205° C.(decomp. recrystallized from                               ethyl acetate and isopropyl ether)                      13                                                                                  ##STR231##      M.p. 205 to 207° C. (recrystallized from                               ethanol, isopropyl ether and n-hexane)                  14                                                                                  ##STR232##      M.p. 163 to 166° C. (recrystallized from                               ethyl acetate and n-hexane)                             15                                                                                  ##STR233##      M.p. 162 to 165° C. (recrystallized from                               ethyl acetate and n-hexane)                             16                                                                                  ##STR234##      M.p. 181 to 183° C. (recrystallized from                               methanol)                                               17                                                                                  ##STR235##      M.p. 208 to 211° C. (recrystallized from                               ethyl acetate)                                          18                                                                                  ##STR236##      M.p. 263 to 265° C. (recrystallized from                               ethanol)                                                19                                                                                  ##STR237##      M.p. 251 to 253° C. (recrystallized from                               methanol)                                               20                                                                                  ##STR238##      M.p. 157 to 159° C. (recrystallized from                               methanol)                                               21                                                                                  ##STR239##      M.p. about 185° C.(decomp. recrystallized                              from ethanol)                                           22                                                                                  ##STR240##      M.p. 158 to 160° C. (recrystallized from                               ethanol)                                                23                                                                                  ##STR241##      M.p. 279 to 283° C. (recrystallized from                               methanol)                                               24                                                                                  ##STR242##      M.p. 194 to 200° C. (recrystallized from                               ethanol)                                                25                                                                                  ##STR243##      M.p. 161 to 163.5° C. (recrystallized from                             ethanol)                                                ______________________________________                                    

PREPARATION 26

(1) A solution of 57.96 g of o-dimethylcarbamoylbenzoic acid intetrahydrofuran is added dropwise to a tetrahydrofuran suspension of34.05 g of sodium borohydride. After the reaction at room temperature,170.3 g of boron trifluoride etherate are added dropwise thereto, andthe mixture is further refluxed. After cooling, a solution of 54 g ofoxalic acid in water and methanol is added thereto, and the mixture isfurther refluxed. The reaction mixture is condensed and extracted withethyl acetate under an alkaline condition. The extract is evaporated toremove the solvent, and the residue is distilled under reduced pressure,whereby 19.04 g of o-dimethylaminomethylbenzyl alcohol are obtained.

B.p. 106° to 109° C. (4 mmHg).

(2) 2.89 g of thionyl chloride are added dropwise to a methylenechloride solution of 2.9 g of the product obtained above. After thereaction at room temperature, the mixture is diluted with ether. Thecrystalline precipitates are collected by filtration, whereby 3.78 g ofo-dimethylaminomethylbenzylchloride hydrochloride are obtained.

M.p. 143° to 147° C.

PREPARATION 27

(1) To a tetrahydrofuran solution of 5.12 g of N-phenylanthranilic acid,32.2 ml of a hexane solution of n-bytyl lithium and a solution of 4.42 gof methyl iodide in tetrahydrofuran are added successively at -60° C.and the mixture is reacted at room temperature. After the reaction,water is added thereto, and the aqueous mixture is extracted with ethylacetate under an acidic condition. The extract is evaporated to removethe solvent, whereby 5.06 g of N-methyl-N-phenyl anthranilic acid areobtained as an oil.

Yield 93%

Mass(m/e): 227 (M⁺)

¹ H-NMR(CDCl₃, δ): 3.22 (s, 3H, NCH₃)

IR ν_(max) ^(liquid) (cm⁻¹): 1690 (COOH).

(2) A solution of 5.06 g of N-methyl-N-phenyl anthranilic acid intetrahydrofuran is added dropwise to a tetrahydrofuran suspension of 1.7g of lithium alminum hydride under ice-cooling. After the reaction atroom temperature, the mixture is cooled in an ice bath. Water and asaturated aqueous sodium sulfate solution are added to the mixture, andinsoluble materials are filtered off. The filtrate is evaporated toremove the solvent, and the residue is purified by silica gel columnchromatography, whereby 4.33 g of o-N-methyl-N-phenylaminobenzyl alcoholare obtained as a colorless oil.

Mass(m/e): 213(M⁺)

¹ H-NMR(CDCl₃,δ): 2.10(t,1H,J=6Hz,OH), 3.21(s,3H,NCH₃),4.56(d,2H,J=6Hz,CH₂ O)

IR ν_(max) ^(liquid) (cm⁻¹): 3360

PREPARATION 28

A solution of 9 g of ethyl o-(1-pyrrolyl)benzoate in ether is addeddropwise to an ether suspension of 2.4 g of lithium alminum hydrideunder ice-cooling. After the reaction, water and a saturated aqueoussodium sulfate solution are added to the mixture, and insolublematerials are filtered off. The filtrate is evaporated to remove thesolvent, and the residue is distilled under reduced pressure, whereby6.3 g of o-(1-pyrrolyl)benzyl alcohol are obtained.

B.p. 120° to 135° C. (3 to 4 mmHg)

Mass(m/e): 173(M⁺)

¹ H-NMR(CDCl₃, δ): 4.52(s,2H,CH₂ O), 6.30 and 6.83 (respectively, t,2H,J=2Hz, ##STR244##

IR ν_(max) ^(liquid) (cm⁻¹): 3380

PREPARATION 29

A mixture of 6.82 g of 2-aminocyclohexanone hydrochloride, 6.21 g of2-pyridylisothiocyanate dimer and 100 ml of toluene is stirred underheating. When the temperature is cooled down to 50° C., 4.61 g oftriethylamine are added dropwise thereto. After the reaction, water isadded to the reaction mixture, and the aqueous mixture is extracted withethyl acetate. The extract is washed with a saturated sodium chloridesolution, dried and evaporated to remove the solvent, whereby 8.2 g ofN-(2-pyridyl)-N'-(2-oxocyclohexyl)thiourea are obtained.

Yield 72%

M.p. 149° to 151° C.

PREPARATION 30

2-aminocyclopentanone hydrochloride is treated in the same manner asdescribed in Preparation 29 to give2-mercapto-1,3a,4,5,6,6a-hexahydro-6a-hydroxy-1-(2-pyridyl)cyclopenta[d]imidazole.

Yield 55%

M.p. 126° to 127° C.

PREPARATION 31

N-(2-pyridyl)-N'-(2-oxocyclohexyl)thiourea is treated in the same manneras described in Example 67-(1) to give1-(2-pyridyl)-4,5,6,7-tetrahydrobenzimidazol-2-thione.

M.p. 203° to 204° C. (recrystallized from ethyl acetate and n-hexane)

PREPARATIONS 32 to 36

2-mercapto-1,3a,4,5,6,6a-hexahydro-6a-hydroxy-1-(2-pyridyl)cyclopenta[d]imidazoleand the corresponding starting compounds are treated in the same manneras described in Example 1-(1) to give the compounds shown in Table 26.

                  TABLE 26                                                        ______________________________________                                         ##STR245##                                                                    ##STR246##                                                                   Pr.  compound (V)                                                             Nos. R              Properties                                                ______________________________________                                        32   N(CH.sub.3).sub.2                                                                            oil                                                       33   N(C.sub.2 H.sub.5).sub.2                                                                     oil                                                       34                                                                                  ##STR247##    oil                                                       35                                                                                  ##STR248##    oil                                                       36                                                                                  ##STR249##    M.p. 155.5 to 158° C.(recrystallized from                              ethyl acetate)                                            ______________________________________                                    

PREPARATION 37

(1) 24.2 g of ethyl o-fluorobenzoate and 9.8 g of imidazole are heatedin the presence of sodium hydride, whereby 23 g of ethylo-imidazolylbenzoate are obtained.

B.p. 165° to 167° C. (2 mmHg)

(2) 5 g of the product obtained above are treated in the same manner asdescribed in Preparation 28 to give 3.4 g of o-imidazolylbenzyl alcohol.

(3) 3.4 g of the product obtained above are treated in the same manneras described in Preparation 26-(2) to give 3.3 g of o-imiazolylbenzylchloride are obtained.

M.p. 160° to 161° C. (recrystallized from ethanol and ether)

PREPARATION 38

(1) A solution of 2.60 g of thiophosgen in 100 ml of ether is added to amixture of 2.48 g of 2-amino-3-methoxypyridine, 4.40 g of sodiumbicarbonate, 100 ml of ether and 50 ml of water under vigorous stirringand ice-cooling. After 30 minutes, organic layer is separated thererom,washed with water, dried and evaporated to remove the solvent. Theresidue is dissolved in chloroform and 2.84 g of 2-aminocyclopentanonehydrochloride are added thereto. 4 ml of triethylamine are addeddropwise thereto and the mixture is stirred at room temperature for 3hours. After the reaction, the reaction mixture is washed with water,dried and evaporated to remove the solvent. The residue isrecrystallized from ethanol, wherby 2.49 g of1,3a,4,5,6,6a-hexahydro-1-(3-methoxy-2-pyridyl)-2-mercapto-6a-hydroxycyclopenta[d]imidazoleare obtained.

Yield 47%

M.p. 189° to 190° C.

(2) 3.15 g of the product obtained above are treated in the same manneras described in Example 67-(1) to give 1.05 g of1,4,5,6-tetrahydro-1-(3-methoxy-2-pyridyl)-2-mercaptocyclopenta[d]imidazoleas prisms.

M.p. 211° to 214° C. (decomp.)

PREPARATION 39

(1) 2-Amino-3-methylpyridine is treated in the same manner as describedin Preparation 38-(1) to give1,3a,4,5,6,6a-tetrahydro-1-(3-methyl-2-pyridyl)-2-mercapto-6a-hydroxycyclopenta[d]imidazole.

M.p. 171° to 174° C.

(2) 2.49 g of the product obtained above are treated in the same manneras described in Example 67-(1) to give 1.15 g of1,4,5,6-tetrahydro-1-(3-methyl-2-pyridyl)-2-mercaptocyclopenta[d]imidazoleas prisms.

M.p. 226° to 228° C. (decomp.)

What is claimed is:
 1. An imidazole derivative of the formula:##STR250## wherein Ring A is a 2-, 3- or 4-pyridyl group which may beunsubstituted or have one or two substituent(s) selected from the groupconsisting of halogen, lower alkyl group, lower alkoxy group,phenyl-lower alkoxy group, nitro group, amino group, lower alkanoylaminogroup, N-lower alkyl-N-lower alkanoylamino group, mono- or di(loweralkyl)amino group, lower alkanoyloxy group, cyano group,trihalogeno-lower alkyl group, trihalogeno-lower alkoxy group, loweralkenyloxy group and hydroxy group; Ring B is a phenyl group which maybe unsubstituted or have a substituent selected from the groupconsisting of a nitro group, amino group, mono- or di(lower alkyl)aminogroup, lower alkanoylamino group, phenylamino group, cycloalkylaminogroup of 3 to 6 ring carbon atoms, N-(tri-loweralkylphenyl)sulfonylamino group, N-lower alkyl-N-(tri-loweralkylphenyl)sulfonylamino group, N-lower alkyl-N-phenylamino group,di(lower alkyl)amino-lower alkyl group, N-lower alkyl-N-loweralkanoylamino group, lower alkylsulfonylamino group, formylamino group,lower alkoxy group, benzoylamino group, and lower alkoxycarbonylaminogroup; l is 0, 1, or 2 and n is 0, 1 or 2 or a salt thereof.
 2. Thecompound according to claim 1 wherein l is 1 or
 2. 3. The compoundaccording to claim 1 wherein l is
 0. 4. The compound according to claim2, in which Ring A is an unsubstituted 2-, 3- or 4-pyridyl group, or a2-, 3-or 4- pyridyl group having one or two substituent(s) selected fromthe group consisting of halogen, lower alkyl group, lower alkoxy group,phenyl-lower alkoxy group, nitro group, amino group, lower alkanoylaminogroup, lower alkanoyloxy group, cyano group, trihalogeno-lower alkylgroup, trihalogeno-lower alkoxy group, lower alkenyloxy group andhydroxy group; and Ring B is phenyl group or a phenyl group having onesubstituent selected from the group consisting of an amino group, amono- or di(lower alkyl)amino group, a lower alkanoylamino group,cyclohexylamino group, a N-lower alkyl-N-phenylamino group, a di(loweralkyl)amino-lower alkyl group, a N-lower alkyl-N-lower alkanoylaminogroup, a lower alkoxy group, benzoylamino group, a loweralkylsulfonylamino group, formylamino group and a loweralkoxycarbonylamino group.
 5. The compound claimed in claim 4 in whichRing A is 2- or 4-pyridyl group or a 2- or 4-pyridyl group having one ortwo substituent(s) selected from the group consisting of C₁₋₄ alkylgroup, C₁₋₄ alkoxy group and a C₇₋₈ phenylalkoxy group; Ring B is anunsubstituted phenyl group or a phenyl group having one substituentselected from the group consisting of amino group, a mono(C₁₋₄alkyl)amino group, a di(C₁₋₄ alkyl)amino group and a C₁₋₄ alkanoylaminogroup; and l is
 1. 6. The compound claimed in claim 5, in which Ring Ais an unsubstituted 2- or 4-pyridyl group, a 3-, 4- or 5-(C₁₋₄alkoxy)-2-pyridyl group, a 3-, 4-, 5- or 6-(C₁₋₄ alkyl)-2-pyridyl group,a 3-(C₇₋₈ phenyl alkoxy)-2-pyridyl group, a 2-(C₁₋₄ alkyl)-4-pyridylgroup, or a 4-(C₁₋₄ alkoxy)-6-(C₁₋₄ alkyl)-2-pyridyl group; and Ring Bis an unsubstituted phenyl group, 2-aminophenyl group, a 2-mono(C₁₋₄alkyl)aminophenyl group, a 2-di(C₁₋₄ alkyl)aminophenyl group or a2-(C₁₋₄ alkanoyl)aminophenyl group.
 7. The compound according to claim6, in which Ring A is an unsubstituted 2- or 4-pyridyl group, a 3-, 4-or 5-methoxy-2-pyridyl group, a 3-, 4-, 5- or 6-methyl-2-pyridyl group,a 3-benzyloxy-2-pyridyl group, a 2-methyl-4-pyridyl group or a4-methoxy-6-methyl-2-pyridyl group; and Ring B is an unsubstitutedphenyl group, 2-aminophenyl group, 2-methylaminophenyl group,2-ethylaminophenyl group, 2-dimethylaminophenyl group,2-diethylaminophenyl group or a 2-acetylaminophenyl group.
 8. Thecompound claimed in claim 5 in which Ring A is an unsubstituted2-pyridyl group or a 2-pyridyl group having one substituent selectedfrom the group consisting of C₁₋₄ alkyl group and C₁₋₄ alkoxy group;Ring B is an unsubstituted phenyl group or a phenyl group having onesubstituent selected from the group consisting of amino group, amono(C₁₋₄ alkyl)amino group and a di(C₁₋₄ alkyl)amino group; and n is 0.9. The compound claimed in claim 8, in which Ring A is 3- or 4-(C₁₋₄alkyl)-2-pyridyl group or 3-(C₁₋₄ alkoxy)-2-pyridyl group; and Ring B is2-aminophenyl group, 2-mono(C₁₋₄ alkyl)aminophenyl group or a 2-di(C₁₋₄alkyl)aminophenyl group.
 10. The compound claimed in claim 9, in whichRing A is a 3- or 4-methyl-2-pyridyl group or 3-methoxy-2-pyridyl group;and Ring B is 2-aminophenyl group, 2-dimethylaminophenyl group or2-diethylaminophenyl group.
 11. The compound claimed in claim 10, whichis 1-(3-methyl-2-pyridyl)-2-[2-(diethylamino)benzylsulfinyl]imidazole ora pharmaceutically acceptable acid addition salt thereof.
 12. Thecompound claimed in claim 10, which is1-(4-methyl-2-pyridyl)-2-[2-(diethylamino)benzylsulfinyl]imidazole or apharmaceutically acceptable acid addition salt thereof.
 13. Apharmaceutical composition for the treatment of ulcers which comprisesan anti-ulcer effective amount of the compound claimed in claim 2 and apharmaceutically acceptable carrier therefor.
 14. A pharmaceuticalcomposition for the treatment of ulcers which comprises an anti-ulcereffective amount of the compound claimed in claim 6 and apharmaceutically acceptable carrier therefor.
 15. A pharmaceuticalcomposition for the treatment of ulcers which comprises an anti-ulcereffective amount of the compound claimed in claim 9 and apharmaceutically acceptable carrier therefor.
 16. A pharmaceuticalcomposition for the treatment of ulcers which comprises an anti-ulcereffective amount of the compound claimed in claim 11 and apharmaceutically acceptable carrier therefor.
 17. A pharmaceuticalcomposition for the treatment of ulcers which comprises an anti-ulcereffective amount of the compound claimed in claim 12 and apharmaceutically acceptable carrier therefor.
 18. A method for treatmentor prophylaxis of peptic ulcer diseases in a warm-blooded animal whichcomprises administering to said warm-blooded animal a pharmaceuticallyeffective amount of the compound claimed in claim
 2. 19. A method forthe treatment or prophylaxis of peptic ulcer diseases in a warm-bloodedanimal which comprises administering to said warm-blooded animal apharmaceutically effective amount of the compound claimed in claim 6.20. A method for treatment or prophylaxis of a peptic ulcer diseases ina warm-blooded animal which comprises administering to said warm-bloodedanimal a pharmaceutically effective amount of the compound claimed inclaim
 9. 21. A method for treatment or prophylaxis of a peptic ulcerdiseases in a warm-blooded animal which comprises administering to saidwarm-blooded animal a pharmaceutically effective amount of the compoundclaimed in claim
 11. 22. A method for treatment or prophylaxis of apeptic ulcer diseases in a warm-blooded animal which comprisesadministering to said warm-blooded animal a pharmaceutically effectiveamount of the compound claimed in claim 12.